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Internally and externally refined composite nano photosensitizer as well as preparation method and application thereof

A photosensitizer and nanotechnology, applied in the field of nanobiomedicine, can solve the problems of lack of targeting, reduced photodynamic therapy efficiency, photosensitizer leakage, etc., to improve energy transfer efficiency, improve photodynamic therapy effect, and improve enrichment degree of effect

Active Publication Date: 2019-03-19
CHANGCHUN INST OF OPTICS FINE MECHANICS & PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, PDT in clinical practice has many deficiencies. For example, due to the influence of excitation light penetration depth, it is only used in the treatment of superficial tumors; due to the random distribution of small molecule photosensitizers in the body, in order to avoid photosensitization of the skin , the patient needs to avoid light in a dark room; in addition, the efficiency of photodynamic therapy is seriously reduced due to the problem of the photosensitizer and its tendency to aggregate; in addition, the small molecule photosensitizer is easy to be cleared quickly and lacks targeting, which also limits its application to a certain extent. develop
Although a variety of new nano-photosensitizers have been disclosed in the field of nanomedicine and applied in the PDT treatment of tumors, focusing on the optimal selection and loading method of the photosensitizer, which is usually loaded by physical adsorption in the loading method, but this method The leakage problem of the photosensitizer in the process of transportation still exists, and the above-mentioned limitation problem involved has not been really solved, and there is no report for the PDT photosensitizer and method realized by the principle of internal and external dual action, and this A nano-platform is the key to solve the problems of PDT penetration depth, transport and PDT efficiency

Method used

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  • Internally and externally refined composite nano photosensitizer as well as preparation method and application thereof
  • Internally and externally refined composite nano photosensitizer as well as preparation method and application thereof
  • Internally and externally refined composite nano photosensitizer as well as preparation method and application thereof

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preparation example Construction

[0032] A kind of preparation method of the compound nano-photosensitizer of the present invention both inside and outside, comprises the following steps:

[0033] Remove the oleic acid (oleylamine) ligand on the surface of the rare earth up-conversion nanoparticles in hydrochloric acid with a pH of 4, and after centrifugal purification, modify with a photosensitizer: dissolve the photosensitizer in DMF solution, add to remove the surface ligand In the rare earth up-conversion nanoparticles in the body, the carboxyl group and aminophosphate group in the photosensitizer and the rare earth cations on the surface of the rare earth up-conversion nanoparticles undergo a coordination binding reaction. After stirring overnight, the excess photosensitive molecules are removed by centrifugation, and the up-conversion nanoparticles are obtained. Photosensitizer: Amphiphilic polymers are used to coat luminescent molecules and up-conversion nano-photosensitizers through hydrophobic-hydropho...

Embodiment 1

[0065] The preparation of embodiment 1 composite nano photosensitizer

[0066] Step 1. Preparation of upconversion nanoparticles NaYF by high temperature pyrolysis 4 :Yb,Er

[0067] Accurately weigh 236.8 mg of yttrium chloride hexahydrate, 77.5 mg of ytterbium chloride hexahydrate, and 76.3 mg of erbium chloride hexahydrate, and add them to a 50-ml three-necked bottle, and add 6 ml of oleic acid and 15 ml of 1-octave ( Carbo)ene; Stir and deoxygenate under argon atmosphere for 30 minutes, heat to 120 degrees to fully dissolve the drug, and then lower it to below 60 degrees, then add methanol dissolved with 100 mg of sodium hydroxide and 148 mg of ammonium fluoride Solution, heated up to 65 degrees to remove methanol; then heated to 300 degrees and kept for 90 minutes; after the reaction was completed, centrifuged once with acetone and ethanol respectively, and the product was dissolved in cyclohexane for later use to obtain upconversion nanoparticles NaYF 4 : Yb, Er.

[00...

Embodiment 2

[0076] The photodynamic therapy (PDT) method of the tumor in the deep tissue of embodiment 2 internal and external

[0077] After dispersing the auxiliary agent for the composite nano-photosensitizer of the present invention, it acts on the tumor site through direct intratumoral injection, and generates PDT under the action of light generated inside and outside; Irradiate for imaging-guided therapy, and irradiate for 0.5 to 15 minutes. The emission wavelength can overlap with the absorption spectrum of the photosensitizer used, and energy transfer can occur.

[0078] CPPO responds to tumor microenvironment H 2 o 2 Exciting the photosensitizer implements internal photodynamic principles such as figure 2 As shown, CPPO and H 2 o 2 The reaction generates a 1,2-dioxanedione intermediate, and when the energy level matches between the HOMO of the photosensitizer (Ps) and the LUMO energy level of the 1,2-dioxanedione intermediate, the PS is directly excited Sensitized oxygen mo...

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Abstract

The invention discloses an internally and externally refined composite nano photosensitizer as well as a preparation method and application thereof and belongs to the technical field of nanometer biomedicine. The preparation method disclosed by the invention comprises the following steps: removing a surface ligand from rare-earth upconversion nanoparticles, and modifying by a photosensitizer to obtain an upconversion nano photosensitizer; and coating luminescence molecules and the upconversion nano photosensitizer by virtue of hydrophobic-hydrophobic interactions by adopting amphiphilic polymers, thereby obtaining the composite nano photosensitizer. The composite nano photosensitizer is capable of simultaneously responding to stimulus of a tumor microenvironment so as to realize internal photodynamic force and external photodynamic force under near-infrared light excitation. By combining the characteristic that hydrogen peroxide and the like is highly expressed in the tumor microenvironment with the characteristic of upconversion emission of near-infrared light excitation, tumors are inhibited in both modes in an internally and externally refined manner. After a covalent or chemical coordination manner on the surface of the rare-earth upconversion nanoparticles is combined with the photosensitizer, the energy transfer efficiency can be improved, the singlet oxygen yield is increased, and the photodynamics therapy effect under external excitation can be effectively improved.

Description

technical field [0001] The invention belongs to the technical field of nano-biomedicine, and in particular relates to a composite nano-photosensitizer capable of both internal and external aspects and its preparation method and application. Background technique [0002] Malignant tumor is one of the major diseases that seriously threaten human life and health. Although the current clinical treatment mainly uses surgery, supplemented by chemotherapy, radiotherapy, targeted therapy and other treatment methods, which have improved the prognosis of patients to a certain extent, the serious side effects cause physical harm, and even tumor recurrence and metastasis. problem still cannot be eliminated. Therefore, it is of great significance to develop new technologies and methods with early diagnosis and higher curative effect and safety. [0003] Photodynamic therapy (PDT) of tumors is a new technology for tumor treatment that was formed in the 1970s, because of its small trauma...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K47/69A61K49/00A61K9/51A61P35/00
CPCA61K9/5138A61K41/0057A61K41/0071A61K41/0076A61K49/0093A61K47/6923A61P35/00A61K2300/00
Inventor 常钰磊张友林涂浪平孔祥贵
Owner CHANGCHUN INST OF OPTICS FINE MECHANICS & PHYSICS CHINESE ACAD OF SCI
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