CN106562930B - A kind of weary oxygen responsiveness Liposomal formulation and the preparation method and application thereof - Google Patents
A kind of weary oxygen responsiveness Liposomal formulation and the preparation method and application thereof Download PDFInfo
- Publication number
- CN106562930B CN106562930B CN201610938917.5A CN201610938917A CN106562930B CN 106562930 B CN106562930 B CN 106562930B CN 201610938917 A CN201610938917 A CN 201610938917A CN 106562930 B CN106562930 B CN 106562930B
- Authority
- CN
- China
- Prior art keywords
- aq4n
- preparation
- chlorin
- liposome
- liposomal formulation
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
-
- 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
- A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to biomedicine technical fields, it is related to a kind of weary oxygen responsiveness Liposomal formulation and its preparation and application, more particularly to weary oxygen responsiveness liposome-AQ4N- chlorin e 6 and its preparation and application, especially it is in enhancing optical dynamic therapy to the application in tumor hypoxia area cell killing.Liposomal formulation provided by the invention is made of liposome, AQ4N and chlorin e 6, uniform particle diameter, it is well dispersed in water, partial size is concentrated mainly on 100nm or so in water, photosensitive molecular and melbine can be loaded simultaneously, it is ideal pharmaceutical carrier, there is good internal pharmacokinetics behavior.Experiment shows that liposome-AQ4N- chlorin e 6 preparation of the present invention has very high enrichment at the position of tumour, it can result in the more serious weary oxygen situation of tumor region after implementing optical dynamic therapy, further AQ4N is promoted to play the killing to anoxic cell, generates good tumour synergistic therapeutic effect.
Description
Technical field
The present invention relates to biomedicine technical field, it is related to a kind of weary oxygen responsiveness Liposomal formulation and its preparation and answers
With, and in particular to liposome-AQ4N- chlorin e 6 and its preparation and application, especially it is in enhancing optical dynamic therapy to swollen
Application in the area Liu Fayang cell killing.
Background technique
Tumour (tumour) refers to body under the effect of the various tumorigenesis factors, and local organization hyperplasia is formed by new life
Object (neogrowth), because this neoformation is in occupancy block-like protrusions more, also referred to as neoplasm (neoplasm).According to new life
The cell characteristics of object and harmfulness degree to body, and tumour is divided into benign tumour and malignant tumour two major classes, and cancer
The as general name of malignant tumour.Compared with benign tumour, malignant growth speed is fast, be in infiltrative growth, Yi Fasheng bleeding,
Necrosis, ulcer etc., and often have DISTANT METASTASES IN, cause human body syntexis, inability, anaemia, loss of appetite, fever and serious internal organs
Function is impaired etc., ultimately causes death.Due to aging of population etc., current China's cancer morbidity, the death rate are in
Sustainable growth trend.The report estimation of world's cancer, Cancer in China number of the infected in 2012 are 306.5 ten thousand, account for about whole world morbidity people
Several 1/5th；Number of cancer deaths is 220.5 ten thousand, accounts for about a quarter of global number of cancer deaths.20 years from now on, I
The morbidity number and death toll of state's cancer will also persistently rise: it is predicted according to International Agency for Research on Cancer, if do not adopted an effective measure, I
The year two thousand twenty is counted in state's pathogenesis of cancer number and death will rise to 4,000,000 people and 3,000,000 people；The year two thousand thirty will rise to 5,000,000 people and
3500000 people.
Since malignant growth is rapid, internal blood vessel growth, be unevenly distributed, be easy to cause oxygen in tumor tissues,
Nutriment is insufficient, and then leads to the cancer cell seriously weary oxygen even necrosis of partial region.Have a large number of studies show that weary in tumour
Oxygen region can generate important influence to the effect of clinically common cancer treatment method (such as: chemotherapy, radiotherapy), be cancer cell
The one of the major reasons of tolerance and treatment of cancer failure are generated to conventional chemotherapy, radiotherapy.The optical dynamic therapy of tumour is
It is a kind of that molecular oxygen in tumour cell being transformed into virose singlet oxygen after respective wavelength laser irradiation using photosensitive molecular
And reach a kind of novel cancer therapies for the treatment of tumour purpose.Since 1970s, the optical dynamic therapy of tumour
It receives everybody because it is without long-term toxic side effect, good selectivity, cheap treatment cost the advantages that and widely pays close attention to.But
It is, a large number of studies show that optical dynamic therapy only has good killing to the cancer cell of oxygen content upper zone in tumor tissues
Effect, and it is limited to the cancer cell killing power in weary oxygen region.Simultaneously as a large amount of oxygen can be consumed during optical dynamic therapy
Gas and blood vessel structure is destroyed, the tumor tissues after optical dynamic therapy can become more weary oxygen, finally be unable to reach expected control
Therapeutic effect.
A large amount of scientist is dedicated to developing drug and the treatment of the novel specificity for tumor hypoxia cell at present
Method, in combination with other conventional cancer treatment methods, to realize that efficient, collaboration to tumour are killed.
Summary of the invention
In view of this, the technical problem to be solved in the present invention is that providing a kind of Liposomal formulation and preparation method thereof and answering
With.The Liposomal formulation of liposome-AQ4N- chlorin e 6 provided by the invention has good enhancing optical dynamic therapy to swollen
The killing effect of the area Liu Fayang cell can generate good tumour synergistic therapeutic effect.
In order to achieve the object of the present invention, the present invention adopts the following technical scheme that.
A kind of Liposomal formulation, that is, liposome-AQ4N- chlorin e 6 preparation, by liposome, AQ4N and chlorin e 6
Composition.
AQ4N is a kind of biological reducing type anoxic cell drug toxicity, structure such as formula 1, in current pre-clinical trials
Impressive antitumous effect is embodied.Research finds that AQ4N itself is low to DNA nucleophilic power, does not have apparent thin
Cellular toxicity, but AQ4 is finally metabolized under the action of its in the cell reductase, and AQ4 can be by inhibiting topoisomerase
The activity of enzyme II and effectively interfere cell Proliferation, generate cytotoxicity.In addition, preclinical phase experiment shows that AQ4N can be effective
Enhance the inhibition of Common Chemotherapy drug (such as: cis-platinum) and radiotherapy to tumour growth.
AQ4N in Liposomal formulation of the present invention is wrapped in the hydrophilic area at liposome center, hydrophobic chlorin e 6
It is loaded in the hydrophobic region of liposome.
Liposomal formulation of the present invention can be effectively enriched in tumor locus, simultaneously because photosensitive molecular chlorin
The presence of e6 (formula 2) makes the Liposomal formulation be effectively applied to optical dynamic therapy.Due to oxygen in optical dynamic therapy
A large amount of consumption of gas cause the serious weary oxygen of tumor region, and the Liposomal formulation releases the AQ4N of cladding, specificity
Killing anoxic cell, final realize kill efficient, the collaboration of tumour.
According to the present invention, in some embodiments, in the Liposomal formulation, the liposome is by two palmityl phosphatide
Phatidylcholine (DPPC), cholesterol (CH) and phosphatidyl-ethanolamine-polyethylene glycol (DSPE-PEG) composition.
In some embodiments, Liposomal formulation of the present invention, partial size are 90~160nm.In some implementations
In example, partial size is 100~160nm.
The present invention also provides liposome-AQ4N- chlorin e 6 preparation preparation method, by two palmityl phosphatidyl gallbladders
Alkali (DPPC), cholesterol (CH), phosphatidyl-ethanolamine-polyethylene glycol (DSPE-PEG) and chlorin e 6 are dissolved in chloroform
It in solution, is dried with nitrogen, carries out liposome extruded film after the stirring of AQ4N solution is added.
Wherein, the AQ4N solution is dissolved in phosphate buffer by AQ4N and being made.
Preferably, the concentration of AQ4N is 10mg/mL in the AQ4N solution.
In some embodiments, two palmityl phosphatidyl gallbladder described in the preparation method of Liposomal formulation of the present invention
Alkali, phosphatidyl-ethanolamine-polyethylene glycol, cholesterol, chlorin e 6 molar ratio be 6:0.5:4:0.5.
According to the present invention, in some embodiments, the lipid obtained in the preparation method of the Liposomal formulation
It is 90~160nm that body-AQ4N- chlorin e 6 preparation, which obtains partial size,.
In some embodiments, in the preparation method of Liposomal formulation of the present invention, the stirring is preferable over 50 DEG C
Stirring.
Experiment shows prepared by the method liposome-AQ4N- chlorin e 6 preparation, passes through tail vein to mouse
Injection, and its internal pharmacokinetics behavior is monitored by Imaging-PAM.Liposome-AQ4N- chlorin e 6 system
Agent can have very high enrichment at the position of tumour.The weary oxygen situation of tumor locus is found by the method for immunofluorescence dyeing
Become after optical dynamic therapy more serious.It was found that the life of tumour can be effectively inhibited after optical dynamic therapy and AQ4N combination
It is long.
Therefore the present invention also provides the Liposomal formulations (liposome-AQ4N- chlorin e 6 preparation) increases in preparation
Locally weary oxygen situation, raising are directed to the application in the drug of tumor hypoxia region cell killing to strong tumor region.
Further, the Liposomal formulation (liposome-AQ4N- chlorin e 6 preparation) is additionally provided to overcome in preparation
Tumor hypoxia, enhance photodynamic therapy drug in application.
Compared with prior art, the present invention provides a kind of Liposomal formulations and the preparation method and application thereof.The present invention mentions
The Liposomal formulation (liposome-AQ4N- chlorin e 6 preparation) of confession is made of, partial size liposome, AQ4N and chlorin e 6
Uniform, well dispersed in water, partial size is concentrated mainly on 100nm or so in water, can load simultaneously photosensitive molecular and
AQ4N is ideal pharmaceutical carrier, has good pharmacokinetics behavior.Experiment shows liposome-AQ4N- of the present invention
Chlorin e 6 preparation has very high enrichment at the position of tumour, and locally weary oxygen situation, raising are directed to swollen enhancing tumor region
The weary oxygen region Execution of tumor, realization efficiently cooperate with killing to tumour.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described.
Fig. 1 shows the transmission electron microscope picture of 2 liposome-AQ4N- chlorin e 6 preparation of embodiment；
Fig. 2 shows the particle diameter distribution of 2 liposome-AQ4N- chlorin e 6 preparation of embodiment in water；Wherein,It indicates
The partial size of liposome-chlorin e 6 (hCe6-liposome) preparation in water；Indicate liposome-AQ4N- dihydro porphin
The partial size of pheno e6 (AQ4N-hCe6-liposome) preparation in water；
Fig. 3 shows the ultraviolet absorption effect figure of 2 liposome-AQ4N- chlorin e 6 preparation of embodiment；Wherein ,-indicate lipid
The UV absorption of body-chlorin e 6 (hCe6-liposome) preparation；-- indicate liposome-AQ4N- chlorin e 6 (AQ4N-
HCe6-liposome) the UV absorption of preparation；
Fig. 4 shows the content of 3 different solutions of embodiment singlet oxygen after the laser irradiation of 660nm；Wherein, whereinShow
Liposome-AQ4N- chlorin e 6 (AQ4N-hCe6-liposome) preparation generates singlet oxygen after the laser irradiation of 661nm
Amount；Show that liposome-chlorin e 6 (hCe6-liposome) generates singlet oxygen after the laser irradiation of 660nm
Amount；Show that phosphate buffer (PBS) generates the amount of singlet oxygen after the laser irradiation of 660nm；
Fig. 5 shows the blood circulation time after 4 mouse injecting lipid body-AQ4N- chlorin e 6 preparation of embodiment；
After Fig. 6 shows 4 mouse injecting lipid body-AQ4N- chlorin e 6 preparation of embodiment, different time points are in tumor locus
Enrichment condition；
Fig. 7 shows the distribution situation of liposome-AQ4N- chlorin e 6 preparation in 4 mouse major organs of embodiment；
Fig. 8 shows detection of the method for 5 immunofluorescence dyeing of embodiment to the weary oxygen changed condition in mouse tumor position, wherein scheming
A is the imaging results figure of Laser Scanning Confocal Microscope, and figure b is fluorescence signal statistical results chart, and wherein abscissa is that different experiments group (is divided
Not are as follows: I, II, III and IV), left side ordinate (green) is the ratio in the area Fa Yang, and right side ordinate (red) is that blood vessel is close
Degree；
Fig. 9 shows the growth curve of mouse tumor tumour after optical dynamic therapy of 6 different grouping of embodiment；Including right
According to group (only infusing physiological saline), optical dynamic therapy group (hCe6- is carried out after injecting lipid body-chlorin e 6 24 hours
liposome+L660nm)；Injecting lipid body-chlorin e 6 and progress optical dynamic therapy group (hCe6- after free AQ4N 24 hours
liposome+free AQ4N+L660nm)；Injecting lipid body-AQ4N- chlorin does not carry out optical dynamic therapy group (AQ4N-Ce6-
liposome)；Optical dynamic therapy group (AQ4N-Ce6-liposome+ is carried out after injecting lipid body-AQ4N- chlorin e 6 preparation
L660nm)。
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical scheme in the embodiment of the invention is clearly and completely described,
Obviously, described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based in the present invention
Embodiment, every other embodiment obtained by those of ordinary skill in the art without making creative efforts, all
Belong to the scope of protection of the invention.
For a further understanding of the present invention, combined with specific embodiments below
The preparation of embodiment 1, liposome-AQ4N- chlorin e 6 preparation
After DPPC, DSPE-PEG, CH, Ce6 are weighed according to the ratio that molar ratio is 6:0.5:4:0.5, it is dissolved in three chloromethanes
In alkane solution, chloroform soln is dried up with nitrogen.It weighs AQ4N and is dissolved in the AQ4N for preparing 10mg/mL in phosphate buffer
Simultaneously the solution of preparation is added in liposome-chlorin e 6 for solution, at 50 DEG C after stirred in water bath 30 minutes, by the rouge of preparation
Plastid-AQ4N- chlorin e 6 preparation extruded film.
The nature examination of embodiment 2, liposome-AQ4N- chlorin e 6 preparation
Qualitative detection is carried out to liposome-AQ4N- chlorin e 6 preparation made from embodiment 1, carries out transmission electricity respectively
Microscopy survey, dynamic light scattering, UV absorption.
Wherein, the result of transmission electron microscope detection is as shown in Figure 1, the results show that liposome-AQ4N- two made from embodiment 1
Hydrogen porphines e6 preparation is in monodisperse status distribution in water, shows liposome-AQ4N- chlorin e 6 preparation produced by the present invention
Uniform particle diameter, it is well dispersed in water.
The result of dynamic light scattering detection is as shown in Fig. 2, the results show that liposome-AQ4N- dihydro made from embodiment 1
Partial size is concentrated mainly on 100nm or so to porphines e6 preparation in water.
UV absorbance detection result is as shown in figure 3, the results show that liposome-AQ4N- chlorin made from embodiment 1
E6 preparation has the characteristic absorption peak of AQ4N at 630nm, there is the characteristic absorption peak of chlorin e 6 at 404nm and 660nm.
The photodynamic activity detection of embodiment 3, liposome-AQ4N- chlorin e 6 preparation
Liposome-AQ4N- chlorin e 6 preparation aqueous solution, the laser irradiation through 660nm are prepared, detection singlet oxygen contains
It is slow to set up liposome-AQ4N- chlorin e 6 aqueous solution group, liposome-chlorin e 6 aqueous solution group, phosphate respectively for amount
Fliud flushing group.As a result see Fig. 4.
Fig. 4 the results show that the solution containing photosensitive molecular chlorin e 6 all produces singlet oxygen after laser irradiation,
It can be used as optical dynamic therapy agent.
Embodiment 4, liposome-AQ4N- chlorin e 6 preparation are injected into the internal behavior after mouse in mouse
By liposome-AQ4N- chlorin e 6 preparation by taking in different time points small in tail vein injection to Mice Body
20 μ L of mouse blood surveys fluorescence after cell pyrolysis liquid dissolution is added, goes out liposome-AQ4N- dihydro according to the value quantitative analysis of fluorescence
The porphines e6 content in mouse blood in different time points, as a result as Fig. 5 is shown.
Liposome-AQ4N- chlorin e 6 preparation has longer blood circulation time to Fig. 5 as the result is shown.
Liposome-AQ4N- chlorin e 6 preparation is passed through in tail vein injection to Mice Body, in small animal imaging system
(CRI) point carries out acquisition picture in real time in different times on, observes liposome-AQ4N- chlorin e 6 preparation in tumour portion
The enriching quantity of position, is as a result shown in Fig. 6.The excitation light source of selection is 661nm, and the time for exposure is 50ms.
Fig. 6 as the result is shown over time, believe by the fluorescence of tumor region liposome-AQ4N- chlorin e 6 preparation
Number gradually increase, tumor locus enrichment increase with time.
Liposome-AQ4N- chlorin e 6 preparation is passed through in tail vein injection to Mice Body, by mouse master after 24 hours
After wanting organ to take out, its fluorescence intensity is measured after weighing, cracking, liposome-is gone out according to the numerical value quantitative analysis of fluorescence intensity
AQ4N- chlorin e 6 distribution situation in Different Organs, is as a result shown in Fig. 7.
Fig. 7 as the result is shown liposome-AQ4N- chlorin e 6 preparation tumor locus enrichment can achieve higher water
It is flat.
The variation of embodiment 5, immunofluorescence dyeing detection tumor hypoxia situation
By liposome-AQ4N- chlorin e 6 preparation through in tail vein injection to tumor-bearing mice body, by mouse after 24 hours
Anesthesia, and with 660nm laser irradiation tumor locus 1 hour.Respectively before laser irradiation, after laser irradiation 5 minutes, 4 hours and
0.6mg/ only weary oxygen fluorescence probe Hypoxyprobe is injected to four groups of mouse peritoneals respectively after 24 hoursTM(pimonidazole
Hydrochloride), mouse tumor is cut rear frozen section after 90 minutes to dye, as a result sees Fig. 8.
The imaging results of Fig. 8 Laser Scanning Confocal Microscope show to be compared to control group, the mice tumor sections after laser irradiation
The area Fa Yang (green) compared with being remarkably reinforced before laser irradiation, and have the tendency that deteriorating over time and further.
The optical dynamic therapy of embodiment 6, tumour
Mouse with breast carcinoma subcutaneous tumor model is divided into five groups, including: first group, control group (only note life
Manage salt water)；Optical dynamic therapy group is carried out after second group, injecting lipid body-chlorin e 6 24 hours；Third group injects lipid
Body-chlorin e 6 and progress optical dynamic therapy group after free AQ4N 24 hours；4th group, injecting lipid body-AQ4N- dihydro
Porphines does not carry out optical dynamic therapy group；5th group, optical dynamic therapy is carried out after injecting lipid body-AQ4N- chlorin e 6 preparation
Group.Mouse is carried out after treating accordingly, the growth of its tumour is measured, as a result sees Fig. 9.
The result shows that the control group that compares, second group, third group and the 4th group of tumour growth have only obtained part and have pressed down
System, and the 5th group of tumour growth has then obtained effective inhibition.Show that liposome-AQ4N- chlorin e 6 preparation can be real
Now the efficient collaboration of tumour is killed.
Claims (10)
1. a kind of Liposomal formulation is made of liposome, AQ4N and chlorin e 6, the AQ4N structure is as shown in Equation 1,
2. Liposomal formulation according to claim 1, which is characterized in that the liposome is by two palmityl phosphatidyl gallbladders
Alkali, cholesterol, phosphatidyl-ethanolamine-polyethylene glycol composition.
3. Liposomal formulation according to claim 1 or 2, which is characterized in that partial size is 90~160nm.
4. the preparation method of Liposomal formulation described in claim 1-3 any one, which is characterized in that by two palmityl phosphatidyls
Choline, cholesterol, phosphatidyl-ethanolamine-polyethylene glycol and chlorin e 6 are dissolved in chloroform soln, are dried with nitrogen, are added
Liposome extruded film is carried out after entering the stirring of AQ4N solution.
5. the preparation method of Liposomal formulation according to claim 4, which is characterized in that the AQ4N solution is dissolved in by AQ4N
It is made in phosphate buffer.
6. the preparation method of Liposomal formulation according to claim 4 or 5, which is characterized in that AQ4N in the AQ4N solution
Concentration be 10mg/mL.
7. according to the preparation method of Liposomal formulation described in claim 4-6 any one, which is characterized in that two palmityl
Phosphatidyl choline, phosphatidyl-ethanolamine-polyethylene glycol, cholesterol, chlorin e 6 molar ratio be 6:0.5:4:0.5.
8. according to the preparation method of Liposomal formulation described in claim 4-7 any one, which is characterized in that partial size be 90~
160nm。
9. Liposomal formulation described in claim 1-3 any one enhances tumor region locally weary oxygen situation, raising in preparation
For the application in the drug of tumor hypoxia region cell killing.
10. Liposomal formulation described in claim 1-3 any one overcomes tumor hypoxia, enhancing photodynamic tumor to control in preparation
Application in the drug for the treatment of.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610938917.5A CN106562930B (en) | 2016-10-24 | 2016-10-24 | A kind of weary oxygen responsiveness Liposomal formulation and the preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610938917.5A CN106562930B (en) | 2016-10-24 | 2016-10-24 | A kind of weary oxygen responsiveness Liposomal formulation and the preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106562930A CN106562930A (en) | 2017-04-19 |
| CN106562930B true CN106562930B (en) | 2019-04-26 |
Family
ID=58536367
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610938917.5A Active CN106562930B (en) | 2016-10-24 | 2016-10-24 | A kind of weary oxygen responsiveness Liposomal formulation and the preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106562930B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108126198B (en) * | 2017-12-26 | 2020-12-08 | 南京鼓楼医院 | W18O49-tirapazamine composite nano particle and preparation method and application thereof |
| CN113368056A (en) * | 2021-04-29 | 2021-09-10 | 重庆医科大学 | Carrier-free nano delivery system loaded with carnosol anthraquinone and preparation method thereof |
| CN113577292B (en) * | 2021-08-03 | 2022-10-18 | 深圳市第二人民医院(深圳市转化医学研究院) | Tumor combined treatment preparation with cell exosome loaded with stimulating reagent and photosensitizer and application thereof |
| CN114028565B (en) * | 2021-11-30 | 2023-03-31 | 江南大学 | 3D-COF drug carrying system for treating breast cancer and preparation method thereof |
-
2016
- 2016-10-24 CN CN201610938917.5A patent/CN106562930B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 生物还原药物AQ4N 在肿瘤治疗增敏中的研究进展;陈如萍;《中国药学杂志》;20100222;第45卷(第4期);241-244 * |
| 肿瘤的光动力治疗研究进展;董虹;《中国药科大学学报》;20160825;第47卷(第4期);377-387 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106562930A (en) | 2017-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106075444B (en) | A kind of Liposomal formulation and the preparation method and application thereof | |
| CN106562930B (en) | A kind of weary oxygen responsiveness Liposomal formulation and the preparation method and application thereof | |
| Munson et al. | Anti-invasive adjuvant therapy with imipramine blue enhances chemotherapeutic efficacy against glioma | |
| Guo et al. | Synchronous delivery of oxygen and photosensitizer for alleviation of hypoxia tumor microenvironment and dramatically enhanced photodynamic therapy | |
| Xiang et al. | Increased photodynamic therapy sensitization in tumors using a nitric oxide-based nanoplatform with ATP-production blocking capability | |
| Yu et al. | Triple-functional albumin-based nanoparticles for combined chemotherapy and photodynamic therapy of pancreatic cancer with lymphatic metastases | |
| Tang et al. | Overcome the limitation of hypoxia against photodynamic therapy to treat cancer cells by using perfluorocarbon nanodroplet for photosensitizer delivery | |
| CN113599520B (en) | Porphyrin lipid-perfluorocarbon nano preparation and preparation method and application thereof | |
| Wang et al. | Photodynamic induced uptake of liposomal doxorubicin to rat lung tumors parallels tumor vascular density | |
| Kato et al. | Electron donors rather than reactive oxygen species needed for therapeutic photochemical reaction of near-infrared photoimmunotherapy | |
| Yu et al. | PPy@ Fe3O4 nanoparticles inhibit the proliferation and metastasis of CRC via suppressing the NF-κB signaling pathway and promoting ferroptosis | |
| Sun et al. | Binary regulation of the tumor microenvironment by a pH-responsive reversible shielding nanoplatform for improved tumor chemo-immunotherapy | |
| Wang et al. | RETRACTED ARTICLE: Copper-based metal–organic framework impedes triple-negative breast cancer metastasis via local estrogen deprivation and platelets blockade | |
| Yang et al. | Synergistic anticancer strategy of sonodynamic therapy combined with PI-103 against hepatocellular carcinoma | |
| Kamoshima et al. | Morphological and histological changes of glioma cells immediately after 5-aminolevulinic acid mediated photodynamic therapy | |
| Ma et al. | Laser‐ignited Lipid peroxidation nanoamplifiers for strengthening tumor photodynamic therapy through aggravating ferroptotic propagation and sustainable high immunogenicity | |
| Tang et al. | Mitoquinone intravitreal injection ameliorates retinal ischemia–reperfusion injury in rats involving SIRT1/Notch1/NADPH axis | |
| Mascaraque-Checa et al. | Metformin overcomes metabolic reprogramming-induced resistance of skin squamous cell carcinoma to photodynamic therapy | |
| Zhang et al. | Moderating hypoxia and promoting immunogenic photodynamic therapy by HER-2 nanobody conjugate nanoparticles for ovarian cancer treatment | |
| Kim et al. | Suppressing cancer by damaging cancer cell DNA using LED irradiation | |
| CN112546226B (en) | Bioluminescent engineered bacterium composition and preparation method and application thereof | |
| Yu et al. | Calcium sulfide based nanoreservoirs elicit dual pyroptosis pathways for enhanced anti-tumor immunity | |
| CN113616809B (en) | Application of supermolecule organic frame material in removing residual medicine in photodynamic therapy | |
| Fan et al. | Indocyanine green-loaded exosomes for image-guided glioma nano-therapy | |
| Xu et al. | Activatable “Matryoshka” nanosystem delivery NgBR siRNA and control drug release for stepwise therapy and evaluate drug resistance cancer |
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 | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20201105 Address after: Unit 102-1, building A4, 218 Xinghu street, Suzhou Industrial Park, Suzhou area, China (Jiangsu) pilot Free Trade Zone, Suzhou City, Jiangsu Province Patentee after: Suzhou Baimai biomedical Co.,Ltd. Address before: 215123 No. 199 benevolence Road, Suzhou Industrial Park, Jiangsu, China Patentee before: Suzhou University |
|
| TR01 | Transfer of patent right |