CN114621746A - Afterglow luminescent nano material and preparation method and application thereof - Google Patents
Afterglow luminescent nano material and preparation method and application thereof Download PDFInfo
- Publication number
- CN114621746A CN114621746A CN202210134630.2A CN202210134630A CN114621746A CN 114621746 A CN114621746 A CN 114621746A CN 202210134630 A CN202210134630 A CN 202210134630A CN 114621746 A CN114621746 A CN 114621746A
- Authority
- CN
- China
- Prior art keywords
- afterglow luminescent
- afterglow
- nano material
- luminescent nano
- chlorin
- 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.)
- Granted
Links
- 239000002086 nanomaterial Substances 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 239000002105 nanoparticle Substances 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 18
- SURLGNKAQXKNSP-DBLYXWCISA-N chlorin Chemical compound C\1=C/2\N/C(=C\C3=N/C(=C\C=4NC(/C=C\5/C=CC/1=N/5)=CC=4)/C=C3)/CC\2 SURLGNKAQXKNSP-DBLYXWCISA-N 0.000 claims abstract description 15
- 239000003960 organic solvent Substances 0.000 claims abstract description 14
- 229920000428 triblock copolymer Polymers 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 11
- 239000007864 aqueous solution Substances 0.000 claims abstract description 8
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 5
- 238000002604 ultrasonography Methods 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 238000012984 biological imaging Methods 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- OYINILBBZAQBEV-UWJYYQICSA-N (17s,18s)-18-(2-carboxyethyl)-20-(carboxymethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18,22,23-tetrahydroporphyrin-2-carboxylic acid Chemical compound N1C2=C(C)C(C=C)=C1C=C(N1)C(C)=C(CC)C1=CC(C(C)=C1C(O)=O)=NC1=C(CC(O)=O)C([C@@H](CCC(O)=O)[C@@H]1C)=NC1=C2 OYINILBBZAQBEV-UWJYYQICSA-N 0.000 claims description 2
- FDKRLXBXYZKWRZ-UWJYYQICSA-N 3-[(21S,22S)-16-ethenyl-11-ethyl-4-hydroxy-12,17,21,26-tetramethyl-7,23,24,25-tetrazahexacyclo[18.2.1.15,8.110,13.115,18.02,6]hexacosa-1,4,6,8(26),9,11,13(25),14,16,18(24),19-undecaen-22-yl]propanoic acid Chemical compound CCC1=C(C2=NC1=CC3=C(C4=C(CC(=C5[C@H]([C@@H](C(=CC6=NC(=C2)C(=C6C)C=C)N5)C)CCC(=O)O)C4=N3)O)C)C FDKRLXBXYZKWRZ-UWJYYQICSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract description 21
- 238000003384 imaging method Methods 0.000 abstract description 18
- 230000001443 photoexcitation Effects 0.000 abstract 1
- 238000004020 luminiscence type Methods 0.000 description 27
- 206010028980 Neoplasm Diseases 0.000 description 21
- 230000005284 excitation Effects 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000000799 fluorescence microscopy Methods 0.000 description 7
- 238000002271 resection Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- 230000003187 abdominal effect Effects 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 238000002189 fluorescence spectrum Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 238000002350 laparotomy Methods 0.000 description 3
- 238000012634 optical imaging Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000004065 semiconductor Substances 0.000 description 3
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N sodium azide Substances [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 230000005283 ground state Effects 0.000 description 2
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 2
- 229960004657 indocyanine green Drugs 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000001748 luminescence spectrum Methods 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 229910052761 rare earth metal Inorganic materials 0.000 description 2
- 150000002910 rare earth metals Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 1
- 229910003668 SrAl Inorganic materials 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- -1 alkali metal aluminate Chemical class 0.000 description 1
- 229920000109 alkoxy-substituted poly(p-phenylene vinylene) Polymers 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000004035 chlorins Chemical class 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000004966 intestinal stem cell Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 229920000553 poly(phenylenevinylene) Polymers 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Images
Classifications
-
- 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
- C09K11/02—Use of particular materials as binders, particle coatings or suspension media therefor
- C09K11/025—Use of particular materials as binders, particle coatings or suspension media therefor non-luminescent particle coatings or suspension media
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0036—Porphyrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0052—Small organic molecules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y20/00—Nanooptics, e.g. quantum optics or photonic crystals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- 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
- C09K2211/1074—Heterocyclic compounds characterised by ligands containing more than three nitrogen atoms as heteroatoms
Landscapes
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nanotechnology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Crystallography & Structural Chemistry (AREA)
- Materials Engineering (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Composite Materials (AREA)
- General Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Luminescent Compositions (AREA)
Abstract
The invention discloses a preparation method of an afterglow luminescent nano material, which comprises the following steps: s1, uniformly mixing a chlorin photosensitizer and an amphiphilic triblock copolymer in an organic solvent, and adding the mixture into water under the condition of continuous ultrasound; wherein the amphiphilic triblock copolymer molecule encapsulates a hydrophobic chlorin photosensitizer, forming nanoparticles dispersed in water; and S2, removing the organic solvent in the aqueous solution, and concentrating the aqueous solution to obtain the afterglow luminescent nano material. The invention also provides the afterglow luminescent nano material prepared by the method and application thereof. The afterglow luminescent nano material provided by the invention solves the problems that the existing organic afterglow luminescent material has poor biodegradability and biological safety, short afterglow luminescent wavelength, poor tissue penetrability, short afterglow luminescent half-life period, pre-photoexcitation before each imaging and the like.
Description
Technical Field
The invention relates to the technical field of nano materials, in particular to an afterglow luminescent nano material and a preparation method and application thereof.
Background
Optical imaging plays an essential role in the field of biomedical imaging with its non-invasiveness, high temporal and spatial resolution and high sensitivity. The imaging-guided tumor resection can help the operator to quickly and accurately judge the position of a focus, judge a cutting edge or avoid important parts. The development of intraoperative imaging technology makes the surgery faster, more accurate and safer, which is of great significance for the prognosis of patients. Currently, optical imaging guided tumor resection has become an attractive imaging strategy in clinical surgery, which can help clinicians to identify tumors more quickly and accurately, and indocyanine green (ICG) has been approved by the Food and Drug Administration (FDA) for clinical fluorescence imaging guided tumor resection.
However, fluorescence imaging, which is a conventional optical imaging method, requires real-time optical excitation, and thus is susceptible to interference of tissue autofluorescence, resulting in a problem of low signal-to-noise ratio. In the tumor resection operation guided by fluorescence imaging, the interference of tissue autofluorescence can be generated due to the real-time light excitation required by fluorescence imaging, so that a higher background signal can be generated, a lower signal-to-background ratio can be caused, the judgment of an operator can be interfered, and the tumor resection effect of the operation can be influenced.
In contrast, afterglow luminescence refers to a phenomenon in which a material continues to emit light after light irradiation is stopped. Owing to its unique luminescence property, afterglow luminescent materials have been widely used in the field of optical diagnostics of biomedicine in recent years. As the afterglow material only needs to be excited by pre-illumination and does not need real-time light excitation, the interference of autofluorescence of biological tissues is reduced, and compared with fluorescence imaging, afterglow imaging has higher signal-to-noise ratio and tissue detection depth, and the advantages make the afterglow imaging optical probe have great potential as a biological imaging optical probe and an ideal imaging mode in imaging-guided tumor resection. At present, the development of organic afterglow luminescent materials is in the beginning stage, and only a few organic afterglow luminescent materials have been reported to have afterglow luminescent properties.
The afterglow luminescent materials at present are divided into inorganic afterglow luminescent materials and organic afterglow luminescent materials, wherein the inorganic afterglow luminescent materials are mostly composed of rare earth metal doped alkali metal aluminate (for example: SrAl)2O4:Eu2+-Dy3+) (ii) a The organic afterglow luminescent materials reported at present can be divided into two main categories, namely semiconductor polymers including poly-p-phenylene vinylene polymers (such as MEH-PPV) and thiophene polymers (such as PFODBT), and co-doped afterglow luminescent nano materials using a photosensitizer as an initiator and a chemiluminescent substance as a luminescent substrate. The inorganic afterglow luminescent material has harsh synthesis conditions and is doped with heavy metals such as rare earth metals, etc., resulting in greater biotoxicity. Compared with inorganic afterglow luminescent materials, the organic afterglow luminescent materials have wider application prospect in the biomedical imaging field due to the advantages of better biocompatibility, adjustable luminescence, simple and convenient synthesis, easy functional modification, low price and the like. As an important organic afterglow luminescent material, the semiconductor polymer still has no advantages of organic small molecule materials in the aspects of biodegradability and biological long-term safety, and the organic afterglow nano material of a multi-doped system is still required to be further explored in the aspect of biological safety due to the complexity of components.
Disclosure of Invention
The invention aims to solve the technical problem of providing a novel afterglow luminescent nano material so as to solve the problems of poor biodegradability and biological safety, short afterglow luminescent wavelength, poor tissue penetrability, short afterglow luminescent half-life, pre-excitation of light before each imaging and the like of the conventional organic afterglow luminescent material.
In order to solve the technical problems, the invention provides the following technical scheme:
the invention provides a preparation method of an afterglow luminescent nano material and researches an afterglow luminescent mechanism thereof, wherein the preparation method comprises the following steps:
s1, uniformly mixing a chlorin photosensitizer and an amphiphilic triblock copolymer in an organic solvent, and quickly adding the mixture into water under the condition of continuous ultrasound; wherein the amphiphilic triblock copolymer molecule encapsulates a hydrophobic chlorin photosensitizer, forming nanoparticles dispersed in water;
and S2, removing the organic solvent in the aqueous solution, and concentrating the aqueous solution to obtain the afterglow luminescent nano material.
Further, in step S1, the chlorin photosensitizer is chlorin e4(Ce4), chlorin e6(Ce6), chlorin p6(Cp6), or pyropheophorbide a (ppa).
Further, in step S1, the two ends of the amphiphilic triblock copolymer are hydrophilic segments, and the middle is a hydrophobic segment.
Further, in step S1, the amphiphilic triblock copolymer is polyoxyethylene-polyoxypropylene-polyoxyethylene (PEG-b-PPG-b-PEG) or distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG).
Further, in step S1, the mass ratio of the chlorin photosensitizer to the amphiphilic triblock copolymer is 1: (100-500).
Further, in step S1, the organic solvent is tetrahydrofuran.
Further, in step S2, the method for removing the organic solvent is: the aqueous solution was purged with a stream of nitrogen to remove the organic solvent.
Further, in step S2, after removing the organic solvent, the nanoparticle solution was concentrated by ultracentrifugation using a 30kDa ultrafiltration tube.
Further, in step S2, the prepared nanoparticle concentrated solution was diluted with 1 XPBS buffer and then stored at 4 ℃ in the absence of light.
The invention also provides the afterglow luminescent nano material prepared by the method.
The invention also provides the application of the afterglow luminescent nano material as a nano probe.
The invention also provides the application of the afterglow luminescent nano material in biological imaging.
Compared with the prior art, the invention has the beneficial effects that:
1. the main body of the organic afterglow luminescent nano material provided by the invention is organic micromolecules, and compared with other afterglow luminescent materials, the organic afterglow luminescent nano material has remarkable advantages in the aspects of biocompatibility, biodegradability, luminescence adjustability and the like.
2. After the light excitation is stopped, the organic afterglow luminescent nano material provided by the invention can emit afterglow luminescence with the wavelength of 680nm, and the wave band is near infrared wavelength, so that the tissue penetrability is better, and the deep tissue imaging is easy to realize.
3. The organic afterglow luminescent nano material provided by the invention can continuously emit light after the light excitation stops, and the luminescent half-life period can reach 1.5 hours, so that the long-time imaging of single excitation can be realized.
4. The organic afterglow luminescent nano material provided by the invention can be used for imaging detection of tiny tumors, and the nano probe can realize detection of tumors with the size of about 3 cubic millimeters at minimum.
Drawings
FIG. 1 is a schematic diagram of a method for synthesizing an afterglow luminescent nano material according to the invention;
FIG. 2 is a diagram showing a hydrated particle size distribution of NPs-Ce4 nanoparticles in 1 XPBS buffer;
FIG. 3 is a transmission electron microscope image of NPs-Ce4 nanoparticles;
FIG. 4 is an absorption spectrum of NPs-Ce4 nanoparticles (5. mu.g/mL) in 1 XPBS buffer;
FIG. 5 is a normalized fluorescence spectrum of NPs-Ce4 nanoparticles in 1 XPBS buffer;
FIG. 6 is a normalized afterglow luminescence spectrum of NPs-Ce4 nanoparticles in 1 XPBS buffer;
FIG. 7 is a graph showing the afterglow luminescence decay curve of NPs-Ce4 nanoparticles (30. mu.g/mL) recorded at 37 ℃;
FIG. 8(a) is a graph produced by NPs-Ce4 (2. mu.g/mL)1O2The amount of (D) was varied with the irradiation time of the halogen lamp, and the fluorescence was enhanced (F/F) by a singlet fluorescent probe SOSG (1. mu.M)0) Represents; (b) is shown as using O2、N2Purging or adding 50% w/w NaN3Afterglow intensity of the former and latter NPs-Ce4 (30. mu.g/mL).
FIG. 9(a) is a schematic representation of halogenUV-Vis absorption spectra before and after NPs-Ce4(5 μ g/mL) was irradiated by a lamp for 30 minutes; (b) HPLC chromatogram at 280nm absorbance detected before and after 30 min irradiation of Ce4 in acetonitrile; (c) mass spectrum of newly formed material, retention time 17.6 minutes; (d) one possible mechanism of Ce4 afterglow luminescence (S)0、S1、T1And ISCs represent the ground state, first excited singlet state, first excited triplet state, and intersystem crossing, respectively);
FIG. 10 is a graph of Ce4 (30. mu.g/mL) in Tetrahydrofuran (THF), Acetonitrile (ACN) and chloroform (CHCl)3) In the above formula, the afterglow luminescence intensity collected after 1 minute of irradiation with a halogen lamp;
FIG. 11 is the signal-to-noise ratio (SNR) for comparison and quantification of afterglow and fluorescence imaging after subcutaneous injection of nanoparticle NPs-Ce4 (25. mu.g/mL, 50. mu.L) solution into miceROI 1-IROI 3/IROI 2-IROI 3(n＝3)；
FIG. 12 is a schematic view showing the detailed process of abdominal metastasis using afterglow luminescence of NPs-Ce 4;
fig. 13 is representative afterglow luminescence images recorded at different time points after intravenous injection of the nanoparticle NPs-Ce4 into 4T1 peritoneal tumor-bearing mice, and the average luminescence intensity of the region of interest (ROI) (n-3);
FIG. 14 is an image of the afterglow and bright field after laparotomy of a tumor-bearing mouse injected intravenously with NPs-Ce4 (200. mu.g/mL, 200. mu.L);
FIG. 15 is a brightfield (up) and persistence (down) image (scale bar represents 5 mm) of a tumor resected under guidance of the persistence signal;
fig. 16 is an H & E stained image of a tumor section according to the image number in fig. 12 (scale bar represents 400 microns).
Detailed Description
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
The present invention is further described below in conjunction with the following figures and specific examples so that those skilled in the art may better understand the present invention and practice it, but the examples are not intended to limit the present invention.
The experimental methods used in the following examples are conventional methods unless otherwise specified, and materials, reagents and the like used therein are commercially available without otherwise specified.
Example 1: preparation of organic afterglow luminescent nano material NPs-Ce4 nano particle and research of afterglow luminescent mechanism
The NPs-Ce4 nano-particle solution is synthesized by a nano-coprecipitation method, and the specific method comprises the following steps:
a mixed tetrahydrofuran solution (1mL) containing chlorin e4(Ce4) (0.15mg/mL) and amphiphilic triblock copolymer polyoxyethylene-polyoxypropylene-polyoxyethylene (PEG-b-PPG-b-PEG) (40mg/mL) was rapidly injected into deionized water (9mL) under continuous vigorous ultrasound. The tetrahydrofuran was slowly removed with a gentle stream of nitrogen. The nanoparticle solution was then concentrated using ultracentrifugation using a 30kDa ultrafiltration tube. Thereafter, the nanoparticle concentrated solution was diluted with 1 × PBS buffer and then stored at 4 ℃ in the absence of light.
FIG. 2 is a graph showing the hydrated particle size distribution of NPs-Ce4 nanoparticles in 1 XPBS buffer. As can be seen from the figure, the particle size of the NPs-Ce4 nano-particles is relatively uniform, and most of the NPs-Ce4 nano-particles are distributed in the range of 10-30 nm.
FIG. 3 is a transmission electron microscope image of NPs-Ce4 nanoparticles. TEM images showed that NPs-Ce4 were nanoparticulated in PBS buffer.
FIG. 4 shows the absorption spectrum of NPs-Ce4 nanoparticles (5. mu.g/mL) in 1 XPBS buffer. As a result, the NPs-Ce4 nanoparticles have absorption peaks at 400nm, 670nm, etc., and can absorb the excitation light in these wavelength bands.
FIG. 5 is a normalized fluorescence spectrum of NPs-Ce4 nanoparticles in 1 XPBS buffer. The results show that the NPs-Ce4 nanoparticles can emit fluorescence with the wavelength of 670 nm.
FIG. 6 is a normalized afterglow luminescence spectrum of NPs-Ce4 nanoparticles in 1 XPBS buffer. The results show that the NPs-Ce4 nanoparticles can emit afterglow luminescence with a wavelength of about 680nm after the light excitation is stopped.
FIG. 7 is a graph showing the decay curve of afterglow luminescence recorded at 37 ℃ for NPs-Ce4 nanoparticles (30. mu.g/mL). The result shows that the NPs-Ce4 nano-particle can continuously emit light after the light excitation is stopped, and the half-life period of afterglow luminescence can reach 1.5 h.
FIG. 8(a) is a graph produced by NPs-Ce4 (2. mu.g/mL)1O2The amount of (D) was varied with the irradiation time of the halogen lamp, and the fluorescence was enhanced (F/F) by a singlet fluorescent probe SOSG (1. mu.M)0) Represents; (b) to use O2、N2Purging or adding 50% w/w NaN3Afterglow intensity of the former and latter NPs-Ce4 (30. mu.g/mL). The results showed that the afterglow luminescence of NPs-Ce4 is closely related to the generation of singlet oxygen and is induced by O-charging2Or N2Or add in1O2Scavenger NaN3All cause the change of afterglow luminance.
FIG. 9 is a study on the mechanism of Ce4 afterglow luminescence. The results of FIG. 9 show that the Ce4 afterglow luminescence process is accompanied by degradation and new substance generation, based on which we propose the afterglow luminescence mechanism of Ce4, that is, Ce4 transfers absorbed light energy to oxygen to generate oxygen1O2Subsequently, subsequently1O2The decomposition of the Ce 4-dioxetane intermediate ultimately leads to afterglow luminescence of chlorins by cycloaddition of an oxyethylene double bond (C ═ C) to form the Ce 4-dioxetane intermediate. Since the afterglow luminescence of Ce4 is highly similar to its corresponding fluorescence spectrum, it is presumed that the energy released by the spontaneous decomposition process of Ce 4-dioxetane promotes Ce4 to enter its excited state Ce4, and finally returns to its ground state by the afterglow luminescence, while Ce4-F is generated.
FIG. 10 shows the afterglow luminescence intensities of Ce4 in different solvent systems. The results in the figure show that the afterglow intensity of Ce4 is different depending on the solvent, because the non-radiative transition of singlet oxygen generated by Ce4 is affected due to the difference of the surrounding environment, resulting in different lifetimes of singlet oxygen molecules. Whereas the longer the lifetime of singlet oxygen, the higher the afterglow intensity. However, when Ce4 is used for a biomolecule probe, the above-mentioned organic solvent cannot be used, and only water is used as a solvent. However, Ce4 is difficult to disperse in water and does not exhibit afterglow luminescent properties in water. In the invention, the amphiphilic triblock copolymer encapsulates the Ce4 molecule, so that the dispersion of Ce4 in a water system is realized, and meanwhile, the introduction of the surface copolymer provides a special environment for singlet oxygen, thereby reducing the non-radiative transition of the singlet oxygen, prolonging the service life of the singlet oxygen, increasing the reaction probability of the singlet oxygen and Ce4, and enabling Ce4 to show afterglow luminescence property in the water system, thereby being used for molecular probes.
Example 2: afterglow imaging guided tumor resection
1. In order to show the advantages of near-infrared afterglow luminescence relative to the conventional fluorescence in the in vivo imaging application, afterglow and fluorescence images are obtained after injecting a pre-irradiated NPs-Ce4 nano particle solution into the subcutaneous tissues of living mice. The signal to noise ratio (SNR) of the different images was then quantified, the results being shown in fig. 11.
As can be seen from the figure, the signal-to-noise ratio of afterglow imaging is more than 26 times that of corresponding fluorescence imaging.
NPs-Ce4 was used to detect different sizes of 4T1 tumors in the mouse intraperitoneal cavity. After NPs-Ce4 was irradiated in advance, NPs-Ce4 was injected into the tail vein of mice, and the signals of the afterglow in the abdominal region were continuously monitored by afterglow imaging, the results of which are shown in FIG. 13. As can be seen from the figure, the intensity of the afterglow signal at the abdominal region of the mouse gradually increases with time.
Laparotomy was performed 2 hours after NPs-Ce4 injection, followed by afterglow imaging and ablation of 6 suspicious lesions under guidance of the afterglow signal. FIG. 14 is an image of the afterglow and the bright field after laparotomy of a tumor-bearing mouse, and FIG. 15 is an image of the bright field (upper) and the afterglow (lower) of a tumor resected under guidance of an afterglow signal, showing that all tissues resected with a suspicious lesion can still emit an afterglow signal after being reactivated with light.
The tumor sections were stained by hematoxylin and eosin (H & E) and the results are shown in fig. 16. As can be seen, the tissue excised under the guidance of the afterglow signal is tumor tissue, and the smallest tumor that can be identified is 3 cubic millimeters.
In conclusion, the invention provides a novel organic afterglow luminescent nano material, the main body of which is organic micromolecules, and compared with the existing semiconductor polymer system and multi-molecule doped system organic afterglow luminescent materials, the afterglow luminescent nano material has better biocompatibility and biodegradability; after the light excitation is stopped, afterglow luminescence with the wavelength of about 680nm can be emitted, and the band is near infrared wavelength, so that the tissue penetrability is better, and the imaging of deep tissues is easy to realize; and the luminescence half-life period of the afterglow luminescence nano material can reach 1.5 hours, so that long-time imaging of single excitation can be realized. The afterglow luminescent nano material is suitable for being used as a nano probe to be applied to biological imaging, and can realize the detection of tumors with the size of about 3 cubic millimeters at minimum.
The above-mentioned embodiments are merely preferred embodiments for fully illustrating the present invention, and the scope of the present invention is not limited thereto. The equivalent substitution or change made by the technical personnel in the technical field on the basis of the invention is all within the protection scope of the invention. The protection scope of the invention is subject to the claims.
Claims (10)
1. The preparation method of the afterglow luminescent nano material is characterized by comprising the following steps:
s1, uniformly mixing a chlorin photosensitizer and an amphiphilic triblock copolymer in an organic solvent, and adding the mixture into water under the condition of continuous ultrasound; wherein the amphiphilic triblock copolymer molecule encapsulates a hydrophobic chlorin photosensitizer, forming nanoparticles dispersed in water;
and S2, removing the organic solvent in the aqueous solution, and concentrating the aqueous solution to obtain the afterglow luminescent nano material.
2. The method for preparing an afterglow luminescent nano-material according to claim 1, wherein in step S1, the chlorin photosensitizer is chlorin e4, chlorin e6, chlorin p6 or pyropheophorbide a.
3. The method for preparing an afterglow luminescent nano material of claim 1, wherein in step S1, both ends of the amphiphilic triblock copolymer are hydrophilic segments, and the middle is a hydrophobic segment.
4. The method for preparing an afterglow luminescent nano material of claim 3, wherein in step S1, the amphiphilic triblock copolymer is polyoxyethylene-polyoxypropylene-polyoxyethylene or distearoylphosphatidylethanolamine-polyethylene glycol.
5. The method for preparing an afterglow luminescent nano material according to claim 1, wherein in step S1, the mass ratio of the chlorin photosensitizer to the amphiphilic triblock copolymer is 1: (100-500).
6. The method as claimed in claim 1, wherein in step S1, the organic solvent is tetrahydrofuran.
7. The method for preparing an afterglow luminescent nano material as claimed in claim 1, wherein in step S2, the method for removing the organic solvent is: the aqueous solution was purged with a stream of nitrogen to remove the organic solvent.
8. An afterglow luminescent nanomaterial manufactured according to the method of any of claims 1-7.
9. The use of the afterglow luminescent nanomaterial of claim 8 as a nanoprobe.
10. The use of the afterglow luminescent nanomaterial of claim 8 in biological imaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210134630.2A CN114621746B (en) | 2022-02-14 | 2022-02-14 | Afterglow luminescent nano material and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210134630.2A CN114621746B (en) | 2022-02-14 | 2022-02-14 | Afterglow luminescent nano material and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114621746A true CN114621746A (en) | 2022-06-14 |
| CN114621746B CN114621746B (en) | 2022-12-06 |
Family
ID=81898848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210134630.2A Active CN114621746B (en) | 2022-02-14 | 2022-02-14 | Afterglow luminescent nano material and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114621746B (en) |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101524326A (en) * | 2009-03-30 | 2009-09-09 | 浙江大学 | Chlorin e6 chitosan-stearic acid graft micelle |
| US20160136289A1 (en) * | 2013-07-12 | 2016-05-19 | The Usa, As Represented By The Secretary, Department Of Health And Human Services | Photoactivatable lipid-based nanoparticles as vehicles for dual agent delivery |
| CN105833289A (en) * | 2016-05-30 | 2016-08-10 | 上海交通大学 | Mitochondrion-targeting nano-drug delivery system and preparation method and application thereof |
| CN109161013A (en) * | 2018-07-06 | 2019-01-08 | 中国人民解放军陆军军医大学 | A kind of original position active oxygen and spontaneous photopolymer material of myeloperoxidase responsiveness, preparation method and applications |
| CN109481680A (en) * | 2019-01-09 | 2019-03-19 | 中国科学院长春光学精密机械与物理研究所 | A kind of inside and outside composite Nano photosensitizer and its preparation method and application minored |
| CN110801431A (en) * | 2018-08-03 | 2020-02-18 | 山东大学 | Construction and application of core-shell type intelligent nano delivery system |
| CN110997012A (en) * | 2017-08-01 | 2020-04-10 | 南洋理工大学 | Polymer nanoparticles for afterglow molecular imaging |
| CN111632144A (en) * | 2020-07-06 | 2020-09-08 | 聊城大学 | High-drug-loading-rate photo-chemotherapy bifunctional nanoparticles and preparation method thereof |
| CN113166642A (en) * | 2018-10-02 | 2021-07-23 | 北卡罗莱纳州立大学 | Polymeric chromophores, compositions comprising the same, and methods of making and using the same |
-
2022
- 2022-02-14 CN CN202210134630.2A patent/CN114621746B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101524326A (en) * | 2009-03-30 | 2009-09-09 | 浙江大学 | Chlorin e6 chitosan-stearic acid graft micelle |
| US20160136289A1 (en) * | 2013-07-12 | 2016-05-19 | The Usa, As Represented By The Secretary, Department Of Health And Human Services | Photoactivatable lipid-based nanoparticles as vehicles for dual agent delivery |
| CN105833289A (en) * | 2016-05-30 | 2016-08-10 | 上海交通大学 | Mitochondrion-targeting nano-drug delivery system and preparation method and application thereof |
| CN110997012A (en) * | 2017-08-01 | 2020-04-10 | 南洋理工大学 | Polymer nanoparticles for afterglow molecular imaging |
| CN109161013A (en) * | 2018-07-06 | 2019-01-08 | 中国人民解放军陆军军医大学 | A kind of original position active oxygen and spontaneous photopolymer material of myeloperoxidase responsiveness, preparation method and applications |
| CN110801431A (en) * | 2018-08-03 | 2020-02-18 | 山东大学 | Construction and application of core-shell type intelligent nano delivery system |
| CN113166642A (en) * | 2018-10-02 | 2021-07-23 | 北卡罗莱纳州立大学 | Polymeric chromophores, compositions comprising the same, and methods of making and using the same |
| CN109481680A (en) * | 2019-01-09 | 2019-03-19 | 中国科学院长春光学精密机械与物理研究所 | A kind of inside and outside composite Nano photosensitizer and its preparation method and application minored |
| CN111632144A (en) * | 2020-07-06 | 2020-09-08 | 聊城大学 | High-drug-loading-rate photo-chemotherapy bifunctional nanoparticles and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| YUYAN JIANG等: "A generic approach towards afterglow luminescent nanoparticles for ultrasensitive in vivo imaging", 《NATURE COMMUNICATIONS》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114621746B (en) | 2022-12-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5875578B2 (en) | Nanoparticles for photodynamic therapy | |
| EP2609935B1 (en) | Switching fluorescent nanoparticle probe and fluorescent particle imaging method using same | |
| KR100825939B1 (en) | A constrast medium comprising nanoparticles formed with amphiphilic polymer binding a near-infrared fluorochrome for diagnosing tumor | |
| CN112851842B (en) | Small-size near-infrared two-region fluorescence imaging contrast agent and preparation method and application thereof | |
| CN103509552B (en) | Functional near-infrared fluorescence nanoparticles and preparation and application thereof | |
| WO2019027370A1 (en) | Polymer nanoparticles for afterglow molecular imaging | |
| Liu et al. | Microwave-assisted one-step rapid synthesis of near-infrared gold nanoclusters for NIRF/CT dual-modal bioimaging | |
| KR20120021632A (en) | Novel manganese oxide nanopaticle and contrast agent comprising the same | |
| WO2012151593A1 (en) | Multifunctional infrared-emitting composites | |
| Plunkett et al. | In vivo deep-tissue microscopy with UCNP/Janus-dendrimers as imaging probes: resolution at depth and feasibility of ratiometric sensing | |
| Francolon et al. | Preparation of core/shell NaYF4: Yb, Tm@ dendrons nanoparticles with enhanced upconversion luminescence for in vivo imaging | |
| CN115040664A (en) | Activated near-infrared two-region fluorescent probe and preparation method and application thereof | |
| KR102582064B1 (en) | Nanoparticles comprising near infrared absorption dye, methods for manufacturing thereof, and uses thereof | |
| An et al. | A reticuloendothelial system-stealthy dye–albumin nanocomplex as a highly biocompatible and highly luminescent nanoprobe for targeted in vivo tumor imaging | |
| Lu et al. | Fabrication of semiconducting polymer-blend dots with strong near-infrared fluorescence and afterglow luminescence for bioimaging | |
| CN114621746B (en) | Afterglow luminescent nano material and preparation method and application thereof | |
| KR101928037B1 (en) | Alginate-based biocompatible amphiphilic polymer functionalized upconversion nanoparticle used for bioimaging | |
| An et al. | Facile synthesis of near-infrared bodipy by donor engineering for in vivo tumor targeted dual-modal imaging | |
| Zhang et al. | Highly biocompatible nanoparticles of au@ fluorescent polymers as novel contrast agent for in vivo bimodality NIR fluorescence/CT imaging | |
| KR20160013474A (en) | A photosensitizer-loaded calcium carbonate hybrid nanoparticle, a preparation method thereof and a composition for ultrasound contrast imaging and photodynamic therapy comprising the same | |
| Yang et al. | NIR/photoacoustic imaging of multitype gallbladder cancer using carboxyl/amino functionalized polymer dots | |
| CN114292639A (en) | Multifunctional nano material based on aggregation-induced emission and MXenes, preparation method and application | |
| CN113698364A (en) | AIE molecular structure with long wavelength and high quantum yield, composition, nanoparticle and application of AIE molecular structure | |
| Zhu et al. | Synthesis of PEGylated gold nanorods (Au NRs) as absorption nanoprobes for near-infrared optical imaging | |
| CN114163988A (en) | Tumor cell optical imaging quantum dot and preparation method thereof, quantum dot nanoprobe and kit |
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 |