PH/reduction dual-sensitive multifunctional nano-micelle for tumor chemotherapy and photothermal combined therapy and application of pH/reduction dual-sensitive multifunctional nano-micelle

A nanomicelle, combined therapy technology, applied in antitumor drugs, drug combinations, medical preparations with non-active ingredients, etc., can solve the problems of tumor cell apoptosis, ablation, necrosis, etc., and achieve enhanced uptake and accelerated drug release. , the effect of high drug loading

Inactive Publication Date: 2018-08-03
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Not only that, overheating can also cause apoptosis, necrosis and ablation of tumor cells

Method used

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  • PH/reduction dual-sensitive multifunctional nano-micelle for tumor chemotherapy and photothermal combined therapy and application of pH/reduction dual-sensitive multifunctional nano-micelle
  • PH/reduction dual-sensitive multifunctional nano-micelle for tumor chemotherapy and photothermal combined therapy and application of pH/reduction dual-sensitive multifunctional nano-micelle
  • PH/reduction dual-sensitive multifunctional nano-micelle for tumor chemotherapy and photothermal combined therapy and application of pH/reduction dual-sensitive multifunctional nano-micelle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Both PCL-ss-PEG-ss-PCL and PCL-acetal-PEG were self-synthesized by the research group (for the synthesis method of PCL-ss-PEG-ss-PCL, please refer to the applicant’s patent application on the same day, patent name: folic acid targeted reduction sensitive carrier Drug polymer nanomicelle and its preparation method and application; PCL-acetal-PEG synthesis method, see the applicant's patent application on the same day, patent name: semi-solid acid-sensitive amphiphilic block copolymer preparation method and its use). PCL-ss-PEG-ss-PCL is polycaprolactone-disulfide bond-polyethylene glycol-disulfide bond-polycaprolactone, molecular weight This example uses PCL 3750 -ss-PEG 7500 -ss-PCL 3750 , but when the molecular weight of the PCL-ss-PEG-ss-PCL copolymer is 12000-16000, it can be prepared when the mass percentage of the PEG hydrophilic segment is >45%. PCL-acetal-PEG is polycaprolactone-acetal-polyethylene glycol, and the molecular weight used in this embodiment is 180...

Embodiment 2

[0060] A method for preparing pH / reduction double-sensitive drug-loaded polymer micelles (co-delivery polymeric micelles, Co-PMs), comprising the following steps:

[0061] (1) First transfer doxorubicin hydrochloride and ICG to hydrophobicity respectively: add 1% (mass percentage of material) doxorubicin hydrochloride to methanol solution containing triethylamine (20 μL triethylamine / 1mg doxorubicin), React at room temperature for 20 hours under magnetic stirring; mix ICG and tetrabutylammonium iodide (1:5.72 mass ratio) in dichloromethane, and react at room temperature for 20 hours under magnetic stirring.

[0062] (2) Fully dissolve PCL-ss-PEG-ss-PCL and PCL-acetal-PEG amphiphilic copolymer 1:1 (mass ratio) in the organic solvent dichloromethane, then add desalted doxorubicin and transfection Mix the hydrophobic ICG solution evenly, remove the organic solvent with a rotary evaporator to form a uniform film on the inner wall of the eggplant-shaped bottle, blow dry the residua...

Embodiment 3

[0075] A method for the preparation of folate-targeted, pH / reduction dual-sensitive drug-loaded polymer micelles (FA Co-PMs). Including the following steps:

[0076] When preparing polymer micelles with folic acid-targeted double drug loading, 0.5%-5% (mass percentage) DSPE-PEG (2000)-NH 2 . According to the same steps as in Example 2 (1), (2), (3) and (4) to prepare the surface with -NH 2 After the drug-loaded polymer micelles of active groups, the folic acid targeting molecules were linked by EDC / NHS reaction. The specific reaction steps are: (1) Weigh the molar ratio of about DSPE-PEG-NH 2 5 times of folic acid, dissolved in 500 μL deionized water. (2) Add EDC with a molar ratio of about 10 times of folic acid and NHS with a molar ratio of 2 times of EDC to activate for 15 min. (3) Add the above-mentioned aminated nanoparticles and react at room temperature for 8 hours under magnetic stirring. The specific reaction molecular structure formula is as follows, the carbox...

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Abstract

The invention relates to a pH / reduction dual-sensitive multifunctional nano-micelle for tumor chemotherapy and photothermal combined therapy and application of the pH / reduction dual-sensitive multifunctional nano-micelle. The pH / reduction dual-sensitive multifunctional nano-micelle is characterized in that a PCL-acetal-PEG polymer with pH sensitive characteristic, a PCL-ss-PEG-ss-PCL polymer withreduction sensitive characteristic and a phospholipid DSPE-PEG-NH2 with an active group are used as raw materials and are blended to prepare a pH / reduction intelligent responsive polymer nano-micelleas a carrier; a chemotherapeutic drug and a photosensitizer coat a hydrophobic core of the micelle; a casing is made of hydrophilic PEG and has the characteristic of long circulation and space stability; a folic acid targeting group is modified on the surface of the micelle by a covalent bond; the drug loading capacity is 4 to 10 percent, and the mass ratio of the chemotherapeutic drug to the photosensitizer is 0.5 to 2; the particle size is smaller than 200 nm. The pH / reduction dual-sensitive multifunctional nano-micelle disclosed by the invention has the advantages of good dispersity, smallparticle size, better photothermal conversion effect and high drug loading capacity and encapsulation efficiency; the effect of improving tumor suppression by tumor targeted administration, fluorescence imaging of a tumor site, pH / reduction triggered drug release and chemotherapy and photothermal combined therapy can be realized; the pH / reduction dual-sensitive multifunctional nano-micelle has a broad clinical application prospect in combined targeting therapy of tumors.

Description

technical field [0001] The present invention relates to a pH / reduction dual-sensitive multifunctional nanomicelle for tumor chemotherapy and photothermal combined therapy and its application, specifically, it has tumor targeting and has dual responsiveness of pH and reduction sensitivity to the tumor microenvironment, and It can efficiently entrap chemotherapy drugs and photosensitizers to achieve synergistic therapeutic effects on tumors. It is a multifunctional hybrid micellar drug delivery system that targets tumor chemotherapy and photothermal combined effects. Background technique [0002] Tumors, especially malignant tumors, seriously threaten human health. Due to their characteristics of invasion, recurrence, metastasis, and infinite proliferation, the treatment of tumors has become a major clinical problem. Chemotherapy is currently the most important means of clinical treatment of tumors, but chemotherapy drugs have disadvantages such as non-specific binding, instab...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/24A61K47/22A61K47/34A61K31/704A61K41/00A61P35/00
CPCA61K9/1075A61K31/704A61K41/0052A61K41/0071A61K47/22A61K47/24A61K47/34A61P35/00A61K2300/00
Inventor 张琳华朱敦皖秦玉樊帆张志明
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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