CN114539232B - PH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof - Google Patents

PH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof Download PDF

Info

Publication number
CN114539232B
CN114539232B CN202210096480.0A CN202210096480A CN114539232B CN 114539232 B CN114539232 B CN 114539232B CN 202210096480 A CN202210096480 A CN 202210096480A CN 114539232 B CN114539232 B CN 114539232B
Authority
CN
China
Prior art keywords
near infrared
photosensitizer
induced emission
emission type
region aggregation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202210096480.0A
Other languages
Chinese (zh)
Other versions
CN114539232A (en
Inventor
王东
肖培宏
唐本忠
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenzhen University
Original Assignee
Shenzhen University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shenzhen University filed Critical Shenzhen University
Priority to CN202210096480.0A priority Critical patent/CN114539232B/en
Publication of CN114539232A publication Critical patent/CN114539232A/en
Application granted granted Critical
Publication of CN114539232B publication Critical patent/CN114539232B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1092—Heterocyclic compounds characterised by ligands containing sulfur as the only heteroatom
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention discloses a pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer and application thereof, wherein the pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer is one of the following chemical structural formulas:
Figure DDA0003490984370000011
Figure DDA0003490984370000012
and
Figure DDA0003490984370000013
wherein R is 1 And R is 2 One selected from hydrogen, methyl and methoxy, R 3 Is that
Figure DDA0003490984370000014
One of them. The pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer provided by the invention has the following advantages: has low phototoxicity to normal tissues and cells and very excellent tumor cell targeting capability; aggregation in physiological environment but no fluorescence quenching problem exists, and the active oxygen generating capacity is enhanced; near infrared light excitation has deeper tissue penetrating capacity, and has very good photo-thermal and photodynamic synergistic treatment effect on a human tumor xenograft (PDX) model and bacterial infection.

Description

PH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof
Technical Field
The invention relates to the technical field of photosensitizers, in particular to a pH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof.
Background
Photodynamic (PDT) and photothermal co-therapy (PTT) are a highly effective and promising approach in recent yearsCompared with the traditional treatment modes such as chemotherapy, radiotherapy and the like, the therapeutic mode of the sexual tumor has the advantages of non-invasiveness, low drug resistance, controllable treatment area selection and the like, and thus the therapeutic mode of the sexual tumor is widely focused by medical researchers. PDT is typically composed of three parts: photosensitizer, light and oxygen are indispensable. The photosensitizer absorbs a photon under irradiation of an excitation light source of a specific wavelength, and then changes from the ground state (S 0 ) Transition to singlet excited state (S 1 ). The excited state molecules are very unstable and can return to the ground state by radiation transitions to produce fluorescence; can also be transferred to an excited triplet state (T) with relatively long lifetime by intersystem crossing 1 ) And then interact with biological substrates or molecular oxygen to produce cytotoxic Reactive Oxygen Species (ROS); or by a non-radiative transition back to the ground state, releasing heat (PTT). Compared with single PDT or PTT treatment, the synergistic treatment can overcome the problems of poor treatment effect caused by tumor hypoxia and heat shock protein caused by PTT treatment, and the like in PDT treatment.
The photosensitizers commonly used at present mainly comprise hematoporphyrin derivatives, phthalocyanine derivatives, chlorophyll a degradation products and the like, most of them have the problem of aggregation-quenched (ACQ), so that the fluorescence and active oxygen generating capacity is reduced, and the clinical treatment effect is seriously affected. In 2001, the professor Tang Benzhong to hong Kong university of science and technology proposed a new concept of "aggregation-induced emission (AIE)", which led to the revolution of luminescent materials. Unlike conventional organic fluorescent dyes, such special compounds do not emit light or fluoresce very weakly in solution, but fluoresce strongly in the aggregated state. The occurrence of the aggregation-induced emission photosensitizer overcomes the limitation of the traditional small organic molecule photosensitizer, and has a plurality of advantages in the fields of tumor fluorescence imaging and treatment. First, aggregation-induced emission photosensitizers generally have good biocompatibility. Secondly, the aggregation-induced emission photosensitizer has the advantages of high general luminous efficiency, large Stokes shift, good light stability and enhanced active oxygen generating capability in an aggregation state. Although the aggregation-induced emission photosensitizers have made breakthrough progress in PDT and PTT treatment in recent years, the problems of normal tissue damage and skin photosensitivity due to the short excitation wavelength and poor tumor targeting have seriously hampered their practical clinical application.
The hot spot area of current photosensitizer research is how to further improve tumor targeting and reduce the side effects of phototherapy. The construction of an intelligent activated photosensitizer for a tumor microenvironment is one of the effective strategies for improving tumor targeting. The pH value of the extracellular fluid of the tumor is between 6.5 and 6.8 and is slightly lower than the pH value of the microenvironment of blood and normal tissues (about 7.4), which provides possibility for developing the pH activated photosensitizer of the tumor. The near infrared two region (NIR-II) has longer emission wavelength (1000-1700 nm), which can remarkably reduce the influence of light scattering and autofluorescence effect when penetrating biological tissues, thereby realizing the anti-tumor treatment of deeper tissues.
Therefore, the development of the near infrared two-region emission aggregation-induced emission luminescence photosensitizer with pH reversible activation has very important research significance.
Disclosure of Invention
In view of the defects of the prior art, the invention aims to provide a pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer and application thereof, and aims to solve the problems of poor targeting and large side effect when the existing photosensitizer is used for tumor treatment.
The technical scheme of the invention is as follows:
a pH-reversibly activated near infrared two-region aggregation-induced emission type I photosensitizer, wherein the pH-reversibly activated near infrared two-region aggregation-induced emission type I photosensitizer is one of the following chemical structural formulas:
Figure BDA0003490984350000031
Figure BDA0003490984350000032
wherein R is 1 And R is 2 One selected from hydrogen, methyl and methoxy, R 3 Is->
Figure BDA0003490984350000033
One of them. .
The pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer, wherein the absorption wavelength of the pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer is 660nm-750nm.
The pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer, wherein the emission wavelength of the pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer is 1000nm-1500nm.
The application of the pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer is characterized in that the pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer is used for preparing a medicine for treating tumor or bacterial infection diseases.
The pH reversibly activates the application of the near infrared two-region aggregation-induced emission type I photosensitizer, wherein the medicament adopts mPEG 2000 -PLGA encapsulates the nanoparticles formed by the infrared two-region aggregation-induced emission type I photosensitizer.
The pH reversibly activates near infrared two-region aggregation-induced emission type I photosensitizer, wherein the medicine exists in unconjugated basic form in blood and normal tissues and exists in fully conjugated acid form at tumor sites.
The beneficial effects are that: compared with the traditional photosensitizer, the pH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer provided by the invention has the following advantages: 1. the phototoxicity to normal tissues and cells is low; 2. has very excellent tumor cell targeting capability; 3. aggregation in physiological environment but no fluorescence quenching problem exists, and the active oxygen generating capacity is enhanced; 4. near infrared light excitation has deeper tissue penetration capability. Specifically, the present invention provides mPEG for photosensitizer 2000 The PLGA has pH responsiveness after being encapsulated into nano particles, the PLGA mainly exists in unconjugated basic form in blood and normal tissues after tail vein injection, radiation transition and non-radiation transition channels are closed under 808nm laser irradiation, the PLGA shows lower active oxygen and photo-thermal generation capacity, and obvious phototoxicity is not realized; when the nanoparticles are applied by EPR effectAfter reaching the tumor part, the photosensitizer mainly exists in a fully conjugated acid form under the condition of pH6.5, and radiation transition and non-radiation transition channels are opened under 808nm laser irradiation, so that the photosensitizer has stronger I-type superoxide anion free radical and photo-thermal generation capacity, and a very good photo-thermal and photodynamic synergistic treatment effect is obtained on a human tumor xenograft (PDX) model and bacterial infection.
Drawings
FIG. 1 is a synthetic route diagram of a novel pH reversible activation near infrared two-region aggregation-induced emission molecule according to an embodiment of the present invention.
Fig. 2 is a nuclear magnetic resonance hydrogen spectrum of the compound 1 prepared in example 1 of the present invention in deuterated chloroform.
FIG. 3 is a nuclear magnetic resonance carbon spectrum of compound 1 prepared in example 1 of the present invention in deuterated chloroform.
FIG. 4 is a nuclear magnetic resonance hydrogen spectrum of compound 2 prepared in example 2 of the present invention in dimethyl sulfoxide.
Fig. 5 is a nuclear magnetic resonance hydrogen spectrum of the compound 4 prepared in example 3 of the present invention in deuterated chloroform.
FIG. 6 is a nuclear magnetic resonance carbon spectrum of compound 4 prepared in example 3 of the present invention in deuterated chloroform.
FIG. 7 is a nuclear magnetic resonance hydrogen spectrum of compound 5 prepared in example 4 of the present invention in deuterated chloroform.
FIG. 8 is a nuclear magnetic resonance carbon spectrum of compound 5 prepared in example 4 of the present invention in deuterated chloroform.
Fig. 9 is a nuclear magnetic resonance hydrogen spectrum of the compound 6 prepared in example 5 of the present invention in deuterated chloroform.
FIG. 10 is a nuclear magnetic resonance carbon spectrum of compound 6 prepared in example 5 of the present invention in deuterated chloroform.
FIG. 11 is a nuclear magnetic resonance hydrogen spectrum of compound 7 prepared in example 6 of the present invention in deuterated chloroform.
FIG. 12 is a nuclear magnetic resonance carbon spectrum of compound 7 prepared in example 6 of the present invention in deuterated chloroform.
FIG. 13 is a chart showing the hydrogen nuclear magnetic resonance spectrum of TTVBI in dimethyl sulfoxide of the compound prepared in example 7 of the present invention.
FIG. 14 is a chart showing the nuclear magnetic resonance of TTVBI in dimethyl sulfoxide of the compound prepared in example 7 of the present invention.
FIG. 15 is a chart showing the hydrogen nuclear magnetic resonance spectrum of the DTVBI of the compound prepared in example 8 of the present invention in dimethyl sulfoxide.
FIG. 16 is a chart showing the nuclear magnetic resonance of DTVBI in dimethyl sulfoxide of the compound prepared in example 8 of the present invention.
FIG. 17 is a nuclear magnetic resonance hydrogen spectrum of the compound DTTVCI prepared in example 9 of the present invention in dimethyl sulfoxide.
FIG. 18 is a nuclear magnetic resonance carbon spectrum of the compound DTTVCI prepared in example 9 of the present invention in dimethyl sulfoxide.
FIG. 19 is a graph showing the ultraviolet absorption spectrum of the pH reversibly activated near infrared two-region aggregation-induced emission molecules in dimethyl sulfoxide prepared in examples 7,8 and 9 of the present invention;
FIG. 20 is a graph showing fluorescence emission spectra of pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in examples 7,8 and 9 of the present invention in dimethyl sulfoxide;
FIG. 21 is 10X 10 prepared in examples 7,8 and 9 of the present invention -6 M TTVBI, DTVBI and DTTVCI are in the mixed system of dimethyl sulfoxide/toluene of different proportions;
FIG. 22 is a DLS map of nanoparticle DTTVBI NPs prepared from pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 of the present invention;
FIG. 23 is a graph showing absorption and fluorescence emission patterns of nanoparticle DTTVBI NPs prepared from pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 in dimethyl sulfoxide;
FIG. 24 is a graph showing the UV-visible absorption spectrum of nanoparticles DTTVBI NPs prepared from pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 in PBS buffer solutions with different pH values;
FIG. 25 is a graph showing pKa values obtained by nonlinear fitting of nanoparticles DTTVBI NPs prepared from pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 of the present invention;
FIG. 26 is a graph showing fluorescence spectra of pH6.5 and pH 7.4 nanoparticle DTTVBI NPs prepared from the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 of the present invention under 808nm laser irradiation using DCFH as an indicator of active oxygen;
FIG. 27 is a graph showing the temperature change of pH6.5 and pH 7.4 DTTVCI NPs at 0.8W 806 nm under laser irradiation at different concentrations prepared from the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 of the present invention;
FIG. 28 is a graph showing the temperature change of 100. Mu.M pH6.5 and pH 7.4 DTTVCI nanoparticles prepared from the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 under different power 808nm laser irradiation;
FIG. 29 is a graph showing the photo-thermal imaging effect of DTTVBI NPs with pH6.5 and pH 7.4 nanoparticles prepared from the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 of the present invention;
FIG. 30 is a graph showing the experimental effect of the nanoparticle DTTVBI NPs prepared from the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 of the present invention on photo-thermal and photodynamic combination therapy of PDX model;
FIG. 31 is a graph showing bacterial viability of nanoparticle BC/DTTVCI NPs prepared from pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 for photothermal and photodynamic combination therapy of E.coli.
FIG. 32 is a schematic diagram showing the mechanism of pH reversible activation of the near infrared two-region aggregation-induced emission molecule and nanoparticle preparation prepared in example 9 of the present invention.
Detailed Description
The invention provides a pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer and application thereof, and the invention is further described in detail below for the purpose, technical scheme and effect of the invention to be clearer and more definite. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The invention provides a pH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer, which is one of the following chemical structural formulas:
Figure BDA0003490984350000071
Figure BDA0003490984350000072
wherein R is 1 And R is 2 One selected from hydrogen, methyl and methoxy, R 3 Is->
Figure BDA0003490984350000073
One of them.
Specifically, the invention designs and synthesizes three types of near infrared two-region aggregation-induced emission type I photosensitizers which can be reversibly activated by tumor pH, the three photosensitizers take triphenylamine or diphenylamine with different substitutions as electron donor and rotor in the structure, take thiophene and double bond with different numbers as pi conjugated bridge, and take ethyl or propane sulfonic acid to replace [ c, d ]]The benzoindole is an electron acceptor, and the constructed photosensitizer absorbs 660nm-750nm of wavelength and emits 1000nm-1500nm of wavelength. The invention provides mPEG for photosensitizer 2000 The PLGA has pH responsiveness after being encapsulated into DTTVB nano particles, wherein the maximum absorption of the prepared DTTVB nano particles is 694nm, the prepared DTTVB nano particles have a strong absorption value at 808nm, the DTTVB nano particles mainly exist in a non-conjugated basic DTTVB-OH structure in blood and normal tissues after tail vein injection, and radiation transition and non-radiation transition channels of the DTTVB nano particles are closed under 808nm laser irradiation, so that the DTTVB nano particles have lower active oxygen and photo-thermal generating capacity and have no obvious phototoxicity; when the nano particles reach the tumor part through EPR effect, the photosensitizer mainly exists in a fully conjugated acid type DTTVB structure under the condition that the pH value of the tumor is 6.5-6.8, and radiation transition and non-radiation transition channels are opened under 808nm laser irradiation, so that the nanometer particle has stronger I-type superoxide anion free radical and photo-thermal generation capacity, and obtains excellent photo-thermal effect on a human tumor xenograft (patent-derived tumor xenograft, PDX) model and bacterial infection,Photodynamic synergistic therapeutic effect.
In some embodiments, there is also provided a use of a pH-reversibly activated near infrared two-region aggregation-induced emission type I photosensitizer, wherein the pH-reversibly activated near infrared two-region aggregation-induced emission type I photosensitizer is used for the manufacture of a medicament for treating a tumor or bacterial infection disease.
In this embodiment, the drug is mPEG 2000 -PLGA encapsulates the nanoparticles formed by the infrared two-region aggregation-induced emission type I photosensitizer, the drug being present in unconjugated basic form in blood and normal tissue and in fully conjugated acid form at the tumor site.
The invention is further illustrated by the following examples:
example 1
As shown in fig. 1 a, at N 2 Under the protection of (1) and 851mg of NaH was added to a solution of 2.0g of 1, 8-naphthalimide in DMF (30 ml), 2.21g of ethyl iodide was slowly added dropwise to the reaction system after the reaction solution was lowered to 0℃and the reaction was continuously stirred at room temperature for 3 hours, ethyl acetate was extracted after the completion of the reaction, the organic phases were combined and dried over anhydrous sodium sulfate, and the residue obtained after concentration under reduced pressure was purified by silica gel column chromatography using petroleum ether/ethyl acetate (100:1.fwdarw.10:1) as an eluent to give 1.20g of compound 1 as a yellow powdery solid in 52% yield. The nuclear magnetic resonance hydrogen spectrum of the compound 1 in deuterated chloroform is shown in figure 2, the nuclear magnetic resonance carbon spectrum of the compound 1 in deuterated chloroform is shown in figure 3, wherein, 1 H NMR(600MHz,CDCl 3 )δ8.04(d,J＝6.6Hz,1H),7.98(d,J＝8.4Hz,1H),7.68(dd,J 1 ＝7.8Hz,J 2 ＝6.6Hz,1H),7.50(d,J＝8.4Hz,1H),7.44(dd,J 1 ＝8.4Hz,J 2 ＝7.2Hz,1H),6.89(d,J＝6.6Hz,1H),3.97(q,J＝7.2Hz,2H),1.37(t,J＝7.2Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ167.83,139.22,130.76,129.19,128.69,128.55,126.93,125.26,124.22,120.23,104.89,35.03,14.13.HRMS(ESI,positive ion mode)calcd for C 13 H 12 NO + 198.0913,found 198.0908.
example 2
As shown in the figure1 a is shown in N 2 Under the protection of (2), 1.20g of compound 1 is dissolved in 25ml of dry tetrahydrofuran solution, then 2.43ml of 3.0M methyl magnesium chloride solution is dropwise added into the reaction solution, the reaction is stirred at 60 ℃ for 1h after the completion of the dropwise addition, 12.16ml of 2M hydrochloric acid solution is added after the reaction solution is cooled to room temperature, tetrahydrofuran is removed by decompression concentration, then 6.08ml of 1M potassium iodide solution is added, and a large amount of red precipitate is precipitated by continuing the stirring reaction for 30min. The solid obtained after filtration was washed with water and ethyl acetate in this order and dried to obtain 1.52g of a crude product of compound 2 as a red solid powder with a yield of 70%. The nuclear magnetic resonance hydrogen spectrum of the compound 2 in dimethyl sulfoxide is shown in figure 4, wherein, 1 H NMR(600MHz,DMSO-d 6 )δ8.98(d,J＝7.2Hz,1H),8.80(d,J＝7.8Hz,1H),8.55(d,J＝7.2Hz,1H),8.45(d,J＝8.4Hz,1H),8.17(t,J＝8.4Hz,1H),8.01(t,J＝7.8Hz,1H),4.71(q,J＝7.8Hz,2H),3.24(s,3H),1.55(t,J＝7.2Hz,3H).HRMS(ESI,positive ion mode)calcd for C 14 H 14 N + 196.1121,found 196.1115.
example 3:
as shown in fig. 1 b, at N 2 Under the protection of (2) bromothiophene 5.8g, diphenylamine 4.0g, sodium t-butoxide 3.4g were dissolved in 80ml of dry toluene solution, and 432mg Pd was added sequentially 2 (dba) 3 And 274mg of tri-tert-butylphosphine tetrafluoroborate. Then the reaction solution was heated to 120℃in an oil bath for 16h. After cooling to room temperature, the solvent was removed by concentration under reduced pressure, and the obtained residue was purified by silica gel column chromatography using petroleum ether/ethyl acetate (200:1→50:1) as an eluent to give 4.20g of compound 4 as a yellow powdery solid in 71% yield. The nuclear magnetic resonance hydrogen spectrum of the compound 4 in deuterated chloroform is shown in fig. 5, the nuclear magnetic resonance carbon spectrum of the compound 4 in deuterated chloroform is shown in fig. 6, wherein, 1 H NMR(400MHz,Methylene Chloride-d 2 )δ7.29(d,J＝5.2Hz,2H),7.26(d,J＝5.2Hz,2H),7.14(dd,J 1 ＝8.8Hz,J 2 ＝1.2Hz,4H),7.05–7.01(m,3H),6.91(dd,J 1 ＝5.6Hz,J 2 ＝5.2Hz,1H),6.74(dd,J 1 ＝1.2Hz,J 2 ＝3.6Hz,1H). 13 C NMR(151MHz,CDCl 3 )δ151.58,148.13,129.25,126.02,122.89,122.44,121.69,120.98.HRMS(ESI,positive ion mode)calcd for C 16 H 14 NS + 252.0841,found 252.0832.
example 4:
as shown in fig. 1 b, at N 2 2.51g of Compound 4 was dissolved in 50ml of dry tetrahydrofuran solution under the protection of (A), and after cooling and stirring at-78℃for 30 minutes, 5.0ml of 2.4M n-butyllithium was slowly added dropwise to the reaction mixture, and the reaction was continued at-78℃for 30 minutes. 3.65g of DMF was then added dropwise to the reaction solution, reacted at-78℃for 30min and then transferred to room temperature for further reaction for 10min. The reaction mixture was quenched with 20ml of water, extracted with dichloromethane, the combined organic phases were dried over anhydrous sodium sulfate, and the residue obtained after concentration under reduced pressure was purified by silica gel column chromatography using petroleum ether/ethyl acetate (50:1→10:1) as eluent to give 2.38g of compound 5 as a yellow powdery solid in 85% yield. The nuclear magnetic resonance hydrogen spectrum of the compound 5 in deuterated chloroform is shown in fig. 7, the nuclear magnetic resonance carbon spectrum of the compound 5 in deuterated chloroform is shown in fig. 8, wherein, 1 H NMR(600MHz,CDCl 3 )δ9.61(s,1H),7.46(d,J＝4.2Hz,1H),7.38–7.35(m,4H),7.28(dd,J 1 ＝9.0Hz,J 2 ＝1.8Hz,4H),7.24–7.21(m,2H),6.39(d,J＝4.2Hz,1H). 13 C NMR(151MHz,CDCl 3 )δ181.57,164.42,146.14,138.48,130.59,129.96,126.30,125.64,112.32.HRMS(ESI,positiveion mode)calcd for C 17 H 14 NOS + 280.0791,found 280.0782.
example 5:
as shown in FIG. 1 c, at 0 ℃, N 2 551mg of potassium t-butoxide was added to a solution of 800mg of compound 5 and 960mg of diethyl 2- (thienylmethyl) phosphonate in dry tetrahydrofuran (40 ml) under the protection of (a), and the reaction solution was allowed to react at room temperature for 16h. After completion of the reaction, 50ml of water was added, extraction was performed with ethyl acetate (75 ml x 3), the combined organic phases were dried over anhydrous sodium sulfate, and the residue obtained after concentration under reduced pressure was purified by silica gel column chromatography using petroleum ether/ethyl acetate (50:1→20:1) as eluent to give 1.0g of compound 6 as yellow powdery solid in 95% yield. The nuclear magnetic resonance hydrogen spectrum of the compound 6 in deuterated chloroform is shown in figure 9, and the nuclear magnetic resonance of the compound 6 in deuterated chloroformThe carbon spectrum is shown in fig. 10, wherein, 1 H NMR(600MHz,Chloroform-d)δ7.32–7.28(m,4H),7.20(d,J＝7.3Hz,4H),7.15(d,J＝4.8Hz,1H),7.08(t,J＝7.4Hz,2H),6.98–6.94(m,3H),6.84(d,J＝15.8Hz,1H),6.80(d,J＝3.9Hz,1H),6.54(d,J＝3.8Hz,1H). 13 C NMR(151MHz,CDCl 3 )δ150.81,147.64,142.77,135.96,129.36,127.74,125.66,125.62,123.98,123.53,123.14,122.20,120.13,119.83.HRMS(ESI,positive ion mode)calcd for C 22 H 18 NS 2 + 360.0875,found 360.0862.
example 6:
as shown in fig. 1 c, at N 2 0.70ml of 2.4M n-butyllithium was slowly added dropwise to a solution of 500mg of Compound 6 in dry tetrahydrofuran (10 ml) at-78℃under the protection of the same, and the reaction was completed at-78℃for 30 minutes. Then, 0.54ml of DMF was added dropwise to the reaction mixture, and the reaction mixture was allowed to react at-78℃for 10 minutes, and then allowed to stand at room temperature for 30 minutes. After the reaction was completed, 10ml of water was added, extraction was performed with ethyl acetate (20 ml x 3), the combined organic phases were dried over anhydrous sodium sulfate, and the residue obtained after concentration under reduced pressure was purified by silica gel column chromatography using petroleum ether/ethyl acetate (50:1→10:1) as eluent to give 360mg of compound 7 as yellow powdery solid in 67% yield. The nmr spectrum of compound 7 in deuterated chloroform is shown in fig. 11, the nmr spectrum of compound 7 in deuterated chloroform is shown in fig. 12, wherein, 1 H NMR(500MHz,CDCl 3 )δ9.81(s,1H),7.60(d,J＝4.0Hz,1H),7.32–7.28(m,4H),7.20(d,J＝7.3Hz,4H),7.15(d,J＝15.7Hz,1H),7.10(t,J＝7.4Hz,2H),6.99(d,J＝4.0Hz,1H),6.89(d,J＝3.9Hz,1H),6.71(d,J＝15.7Hz,1H),6.48(d,J＝4.0Hz,1H). 13 C NMR(151MHz,CDCl 3 )δ182.47,153.51,152.86,147.33,140.86,137.59,133.28,129.51,128.57,126.71,125.82,124.22,123.79,118.31,117.81.HRMS(ESI,positive ion mode)calcd for C 23 H 18 NOS 2 + 388.0824,found 388.0812.
example 7:
as shown in fig. 1 a, at N 2 Under the protection of (2), 91mg of Compound 2 and 100mg of Compound 3 were dissolved in 2ml of glacial acetic acid, followed by the sequential addition of 0.2ml of triethylamine0.2ml of acetic anhydride was reacted at 60℃in an oil bath for 1 hour. After the reaction was completed, the reaction mixture was cooled to room temperature, and a large amount of green precipitate was precipitated by dropwise addition of 20ml of anhydrous diethyl ether, and the solid residue obtained after filtration was purified by silica gel column chromatography using methylene chloride/methanol (50:1→10:1) as an eluent to give 95mg of a black powdery solid compound TTVBI in 40% yield. The nuclear magnetic resonance hydrogen spectrum of the compound TTVBI in deuterated chloroform is shown in figure 13, the nuclear magnetic resonance carbon spectrum of the compound TTVBI in deuterated chloroform is shown in figure 14, wherein, 1 H NMR(600MHz,DMSO-d 6 )δ9.26(d,J＝7.5Hz,1H),9.03(d,J＝15.4Hz,1H),8.65(d,J＝8.0Hz,1H),8.27(dd,J 1 ＝7.8,J 2 ＝2.6Hz,2H),8.21(d,J＝4.1Hz,1H),8.14(t,J＝7.7Hz,1H),7.94–7.90(m,1H),7.77(d,J＝4.1Hz,1H),7.75–7.72(m,2H),7.56(d,J＝15.4Hz,1H),7.42–7.37(m,4H),7.18(t,J＝7.5Hz,2H),7.14(d,J＝7.3Hz,4H),6.98(d,J＝8.8Hz,2H),4.79(q,J＝7.3Hz,2H),1.51(t,J＝7.3Hz,3H). 13 C NMR(151MHz,DMSO-d 6 )δ160.06,154.73,149.09,146.17,145.06,139.93,139.30,138.87,136.15,134.08,130.81,129.97,129.91,129.13,128.90,127.72,127.55,125.67,125.41,125.19,124.57,123.25,121.12,117.96,111.61,40.90,15.33.HRMS(ESI,positive ion mode)calcd for C 37 H 29 N 2 S + 533.2046,found 533.2034.
example 8:
as shown in fig. 1 b, at N 2 Under the protection of (2), 116mg of compound 2 and 100mg of compound 5 were dissolved in 2.5ml of glacial acetic acid, followed by the sequential addition of 0.25ml of triethylamine and 0.25ml of acetic anhydride, and reacted at 60℃in an oil bath for 3 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, and a large amount of green precipitate was precipitated by dropwise addition of 20ml of anhydrous diethyl ether, and the solid residue obtained after filtration was purified by silica gel column chromatography using methylene chloride/methanol (50:1→10:1) as an eluent to give 45mg of a black powdery solid compound DTVBI in 22% yield. The nuclear magnetic resonance hydrogen spectrum of the compound DTVBI in deuterated chloroform is shown in figure 15, the nuclear magnetic resonance carbon spectrum of the compound DTVBI in deuterated chloroform is shown in figure 16, wherein, 1 H NMR(600MHz,DMSO-d 6 )δ8.98(d,J＝7.2Hz,1H),8.88(d,J＝14.4Hz,1H),8.38(d,J＝7.8Hz,1H),8.19(s,1H),7.97–7.92(m,2H),7.78(d,J＝7.8Hz,1H),7.73(t,J＝7.8Hz,1H),7.59(d,J＝4.4Hz,8H),7.49–7.46(m,2H),6.88(d,J＝14.4Hz,1H),6.56(d,J＝4.7Hz,1H),4.47(q,J＝7.3Hz,2H),1.33(t,J＝7.1Hz,3H). 13 C NMR(151MHz,DMSO)δ174.47,170.99,156.73,144.44,144.36,139.66,132.99,130.59,130.55,130.07,129.95,129.58,129.21,128.57,128.53,126.45,124.92,124.00,115.17,112.59,104.97,40.05,14.41.HRMS(ESI,positive ion mode)calcd for C 31 H 25 N 2 S + 457.1733,found 457.1722.
example 9:
as shown in fig. 1 c, at N 2 Under the protection of (2), 84mg of compound 2 and 100mg of compound 7 were dissolved in 2.0ml of glacial acetic acid, followed by the sequential addition of 0.2ml of triethylamine and 0.2ml of acetic anhydride, and reacted at 60℃in an oil bath for 3 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, and a large amount of green precipitate was precipitated by dropwise addition of 20ml of anhydrous diethyl ether, and the solid residue obtained after filtration was purified by silica gel column chromatography using methylene chloride/methanol (50:1→10:1) as an eluent to give 81mg of a black powdery solid compound DTTVBI in 45% yield. The nuclear magnetic resonance hydrogen spectrum of the compound DTTVCI in deuterated chloroform is shown in figure 17, the nuclear magnetic resonance carbon spectrum of the compound DTTVCI in deuterated chloroform is shown in figure 18, wherein, 1 H NMR(500MHz,CD 3 OD-d 4 :CD 2 Cl 2 -d 2 ＝1:1)δ8.89(d,J＝7.5Hz,1H),8.76(d,J＝15.0Hz,1H),8.42(d,J＝8.0Hz,1H),8.06(d,J＝8.0Hz,1H),8.03(d,J＝8.0Hz,1H),7.88–7.85(m,2H),7.80(t,J＝8.0Hz,1H),7.36(d,J＝9.0Hz,1H),7.34–7.31(m,4H),7.23–7.21(m,4H),7.18–7.14(m,3H),7.12(d,J＝15.0Hz,1H),7.04(d,J＝4.1Hz,1H),6.74(d,J＝15.4Hz,1H),6.42(d,J＝4.1Hz,1H),4.61(q,J＝7.3Hz,2H),1.63(t,J＝7.3Hz,3H). 13 C NMR(126MHz,CD 3 OD-d 4 :CD 2 Cl 2 -d 2 ＝1:1)δ159.54,158.10,157.69,147.26,144.96,141.67,140.12,139.87,136.14,133.09,132.32,132.12,131.35,131.05,130.52,130.42,130.11,129.09,128.97,126.64,125.73,125.06,124.83,117.06,116.78,116.29,110.03,41.46,15.33.HRMS(ESI,positive ion mode)calcd for C 37 H 29 N 2 S 2 + 565.1767,found 565.1753。
example 10
The ultraviolet absorption spectra of the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in examples 7 to 9 were respectively tested, and the results are shown in fig. 19, and it can be seen from fig. 19 that the maximum absorption values of TTVBI, DTVBI and DTTVBI in dimethyl sulfoxide are located at 660nm,694nm and 750nm, respectively.
The fluorescence emission spectra of the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in examples 7 to 9 were respectively tested, and the results are shown in fig. 20, and it can be seen from fig. 20 that the emission ranges of TTVBI, DTVBI and DTTVBI in dimethyl sulfoxide cover the near infrared I region and the II region.
10x 10 prepared in examples 7,8 and 9 were tested respectively -6 As shown in fig. 21, it can be seen from fig. 21 that TTVBI, DTVBI and DTTVBI have typical aggregation-induced emission effects.
Example 11
With mPEG 2000 PLGA DTTVBI in example 9 was encapsulated into nanoparticles.
The DLS pattern of the nanoparticles of example 11 was tested, and the results are shown in FIG. 22. It can be seen from FIG. 22 that the prepared nanoparticles were dispersed uniformly with a particle size of 140-165 nm.
The absorption and fluorescence emission spectra of the nanoparticle DTTVCI NPs in dimethyl sulfoxide in example 11 were tested, and the result is shown in FIG. 23, and it can be seen from FIG. 23 that the maximum absorption value of the DTTVCI NPs is 694nm and the maximum emission is 1000nm.
The ultraviolet-visible absorption spectrum of the nanoparticle DTTVBI NPs of example 11 in PBS buffer solutions of different pH values was tested, and the result is shown in fig. 24, and it can be seen from fig. 24 that as the pH value increases from 4 to 10, the absorption value of the prepared nanoparticle increases around 425nm, and the absorption value decreases at 694nm, indicating that the nanoparticle has obvious pH responsiveness.
The pKa value graph obtained by nonlinear fitting of the nanoparticle DTTVBI NPs in example 11 was tested, and the result is shown in fig. 25, and it can be seen from fig. 25 that the pKa value of the nanoparticle is 6.94.
The fluorescence spectrum of pH6.5 and pH 7.4 nanoparticles DTTVCI NPs prepared by the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 under 808nm laser irradiation with DCFH as an active oxygen indicator was tested, and the results are shown in FIG. 26, it can be seen from FIG. 26 that pH6.5 DTTVCI NPs have high active oxygen generating capacity, while Ph 7.4 DTTVCI NPs have weaker active oxygen generating capacity, indicating that the nanoparticles prepared under physiological conditions have no photosensitivity and have little damage to normal tissues and cells.
The temperature change patterns of different concentrations of pH6.5 and pH 7.4 DTTVCI NPs prepared by the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 under the irradiation of laser light of 0.8W 806 nm are tested, and as a result, as shown in FIG. 27, it can be seen from FIG. 27 that the pH6.5 DTTVCI NPs has very excellent photo-thermal effect, and the temperature can be raised to 65 ℃ at the highest; the pH 7.4 DTTVCBI NPs has poor photo-thermal effect, and the temperature can only be raised to 43 ℃, which indicates that the nano particles prepared under physiological conditions have no photo-thermal killing effect and have little damage to normal tissues and cells.
The temperature change patterns of 100um pH6.5 and pH 7.4DTTVBI nanoparticles prepared from the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 under different power 808nm laser irradiation were tested, and as a result, as shown in fig. 28, it can be seen from fig. 28 that pH6.5 DTTVBI NPs have more excellent photo-thermal effects than pH 7.4DTTVBI NPs under the same power.
The photo-thermal imaging effect graphs of pH6.5 and pH 7.4 nanoparticle DTTVBI NPs prepared from the pH reversibly activated near infrared two-region aggregation-induced emission molecules prepared in example 9 were tested, and as a result, as shown in fig. 29, it can be seen from fig. 29 that pH6.5 DTTVBI NPs has a more excellent photo-thermal imaging effect than pH 7.4DTTVBI NPs.
The experimental graph of the effect of the nanoparticle DTTVCI NPs prepared from the pH reversibly activated near infrared two-region aggregation-induced emission molecules in the PDX model photo-thermal and photodynamic combined treatment is tested, and the result is shown in FIG. 30, and it can be seen from FIG. 30 that the DTTVCI NPs can effectively inhibit the growth of PDX tumors and have very good tumor targeting and biocompatibility.
The bacterial survival rate diagram of the nano particles BC/DTTVCI NPs prepared by the pH reversibly activated near-infrared two-region aggregation-induced emission molecules prepared in the example 9 is tested for the photo-thermal and photodynamic combined treatment of the escherichia coli, and the result is shown in the figure 31, the BC/DTTVCI NPs with the concentration of 150 mu M can realize the efficient killing of the escherichia coli, the antibacterial rate is as high as more than 95%, and the nano particles BC/DTTVCI NPs have very good PDT/PTT synergistic antibacterial effect.
The preparation process and the mechanism of pH reversible activation of the nanoparticle DTTVB NPs of the pH reversible activated near infrared two-region aggregation-induced emission molecule prepared in the example 9 are drawn, and the result is shown in a graph 32, and as can be seen from the graph 32, the photosensitizer mainly exists in a non-conjugated basic DTTVB-OH structure under normal physiological conditions and has no obvious photosensitivity; under the slightly acidic condition of the tumor, the photosensitizer mainly exists in a fully conjugated acid type DTTVB structure, and has excellent PDT/PTT synergistic treatment effect.
It is to be understood that the invention is not limited in its application to the examples described above, but is capable of modification and variation in light of the above teachings by those skilled in the art, and that all such modifications and variations are intended to be included within the scope of the appended claims.

Claims (6)

1. The pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer is characterized in that the pH reversible activation near infrared two-region aggregation-induced emission type I photosensitizer is one of the following chemical structural formulas:
Figure QLYQS_1
、/>
Figure QLYQS_2
and->
Figure QLYQS_3
Wherein R is 1 And R is 2 One selected from hydrogen, methyl and methoxy, R 3 Is->
Figure QLYQS_4
。
2. The pH reversibly activated near infrared two region aggregation-induced emission type I photosensitizer according to claim 1, wherein the pH reversibly activated near infrared two region aggregation-induced emission type I photosensitizer has an absorption wavelength of 660nm to 750nm.
3. The pH reversibly activated near infrared two region aggregation-induced emission type I photosensitizer according to claim 1, wherein the emission wavelength of the pH reversibly activated near infrared two region aggregation-induced emission type I photosensitizer is 1000nm to 1500nm.
4. Use of a pH-reversibly activated near infrared two-region aggregation-induced emission type I photosensitizer according to any one of claims 1-3 for the preparation of a medicament for the treatment of a tumor or bacterial infection disease.
5. The use of a near infrared two-region aggregation-induced emission type I photosensitizer with reversible pH activation according to claim 4, wherein the drug is mPEG 2000 -PLGA encapsulates the nanoparticles formed by the infrared two-region aggregation-induced emission type I photosensitizer.
6. The use of a near infrared two-region aggregation-induced emission type I photosensitizer with reversible pH activation according to claim 4, wherein the drug is present in unconjugated basic form in blood and normal tissues and in fully conjugated acid form at the tumor site.
CN202210096480.0A 2022-01-26 2022-01-26 PH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof Active CN114539232B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210096480.0A CN114539232B (en) 2022-01-26 2022-01-26 PH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210096480.0A CN114539232B (en) 2022-01-26 2022-01-26 PH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof

Publications (2)

Publication Number Publication Date
CN114539232A CN114539232A (en) 2022-05-27
CN114539232B true CN114539232B (en) 2023-04-28

Family

ID=81673921

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210096480.0A Active CN114539232B (en) 2022-01-26 2022-01-26 PH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof

Country Status (1)

Country Link
CN (1) CN114539232B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116947792B (en) * 2023-09-20 2023-12-26 内蒙古大学 Aggregation-induced emission type photosensitizer with I-type active oxygen and photo-thermal generation capacity and preparation method and application thereof
CN117599261A (en) * 2024-01-23 2024-02-27 柔脉医疗(深圳)有限公司 Visual artificial vascular stent and preparation method and application thereof

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4756987A (en) * 1985-11-27 1988-07-12 Mitsubishi Chemical Industries Limited Optical recording medium
JP2016047801A (en) * 2014-08-27 2016-04-07 公立大学法人首都大学東京 Triphenylamine-bound dibenzopyrromethene-based dye as sensitizer for dye-sensitized solar cell
CN111978313A (en) * 2020-08-28 2020-11-24 深圳大学 Multi-modal light diagnosis and treatment agent with aggregation-induced emission property and preparation and application thereof
CN113402514A (en) * 2021-05-17 2021-09-17 南方医科大学 Organic dye compound and preparation method and application thereof
CN113429421A (en) * 2021-07-19 2021-09-24 南京诺源医疗器械有限公司 Preparation method of organic small-molecule fluorescent probe
CN113461707A (en) * 2021-08-03 2021-10-01 南京诺源医疗器械有限公司 Preparation method of near-infrared two-region fluorescent micromolecules
CN113717169A (en) * 2021-09-03 2021-11-30 南通大学 N, N-diphenylamino-modified beta-carboline indolium salt, preparation method and application
CN113831331A (en) * 2020-06-08 2021-12-24 香港科技大学 Near-infrared two-region aggregation-induced emission molecule for multi-modal imaging and diagnosis and treatment and application thereof

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4756987A (en) * 1985-11-27 1988-07-12 Mitsubishi Chemical Industries Limited Optical recording medium
JP2016047801A (en) * 2014-08-27 2016-04-07 公立大学法人首都大学東京 Triphenylamine-bound dibenzopyrromethene-based dye as sensitizer for dye-sensitized solar cell
CN113831331A (en) * 2020-06-08 2021-12-24 香港科技大学 Near-infrared two-region aggregation-induced emission molecule for multi-modal imaging and diagnosis and treatment and application thereof
CN111978313A (en) * 2020-08-28 2020-11-24 深圳大学 Multi-modal light diagnosis and treatment agent with aggregation-induced emission property and preparation and application thereof
CN113402514A (en) * 2021-05-17 2021-09-17 南方医科大学 Organic dye compound and preparation method and application thereof
CN113429421A (en) * 2021-07-19 2021-09-24 南京诺源医疗器械有限公司 Preparation method of organic small-molecule fluorescent probe
CN113461707A (en) * 2021-08-03 2021-10-01 南京诺源医疗器械有限公司 Preparation method of near-infrared two-region fluorescent micromolecules
CN113717169A (en) * 2021-09-03 2021-11-30 南通大学 N, N-diphenylamino-modified beta-carboline indolium salt, preparation method and application

Also Published As

Publication number Publication date
CN114539232A (en) 2022-05-27

Similar Documents

Publication Publication Date Title
Wang et al. Progress and trends of photodynamic therapy: From traditional photosensitizers to AIE-based photosensitizers
Swamy et al. Near Infrared (NIR) absorbing dyes as promising photosensitizer for photo dynamic therapy
Li et al. Recent advances in the development of near-infrared organic photothermal agents
Liang et al. Self-quenched ferrocenyl diketopyrrolopyrrole organic nanoparticles with amplifying photothermal effect for cancer therapy
CN114539232B (en) PH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof
Wang et al. Enhancing near-infrared AIE of photosensitizer with twisted intramolecular charge transfer characteristics via rotor effect for AIE imaging-guided photodynamic ablation of cancer cells
Cui et al. Stable π-radical nanoparticles as versatile photosensitizers for effective hypoxia-overcoming photodynamic therapy
Feng et al. Anti-photobleaching cyanine-based nanoparticles with simultaneous PET and ACQ effects for improved tumor photothermal therapy
Li et al. Advancing biomedical applications via manipulating intersystem crossing
CN111689955A (en) Naphthothiadiazole free radical type photosensitizer and preparation method and application thereof
Zhang et al. Diketopyrrolopyrrole derivatives-based NIR-II fluorophores for theranostics
CN110003461A (en) Two pyrrole derivatives of fluorine boron and its preparation method and application of more iodine modifications
CN114213419A (en) Fluorescent probe with fluorescence imaging and I-type photodynamic/photothermal cancer cell killing activities as well as preparation method and application thereof
Deng et al. Single molecular-based nanoparticles with aggregation-induced emission characteristics for fluorescence imaging and efficient cancer phototherapy
Zhao et al. Recent advances and prospects in organic molecule-based phototheranostic agents for enhanced cancer phototherapy
Yin et al. The tumor phototherapeutic application of nanoparticles constructed by the relationship between PTT/PDT efficiency and 2, 6-and 3, 5-substituted BODIPY derivatives
CN105585872B (en) Asymmetric near-infrared cyanine dye and preparing method and application thereof
CN115304534A (en) Photodynamic photosensitizer and preparation method and application thereof
Wang et al. Reasonable design of NIR AIEgens for fluorescence imaging and effective photothermal/photodynamic cancer therapy
Li et al. Triphenylamine flanked boron difluoride formazanate for NIR-II fluorescence imaging-guided photothermal therapy
Xu et al. Highly bright stable organic radicals encapsulated by amphiphilic polypeptide for efficient near-infrared phototheranostics
Zhu et al. Reviewing the evolutive ACQ‐to‐AIE transformation of photosensitizers for phototheranostics
CN117919443A (en) Covalent organic framework combining diagnosis of hypoxia-activated therapy and self-accelerating drug release to coordinate cancer immunotherapy
Lv et al. Configuration-mediated excited-state energy dissipation in metal-bridged dimeric DA fluorophores for enhanced photothermal therapy
Li et al. Synchronously manipulating absorption and nonradiative transition of croconaine via donor engineering for efficient NIR-II photothermal theranostics

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant