A mitochondria-targeted nanophotosensitive immune compound drug and its preparation method and application

An immune complex and mitochondrial technology, applied in nanomedicine, nanotechnology for materials and surface science, drug combination, etc., can solve problems such as time-consuming, lack of clinical-grade vaccine standard solutions, and low migration rate of dendritic cells

Active Publication Date: 2020-06-16
UNIV OF ELECTRONICS SCI & TECH OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this method has the characteristics of feasible principle and direct operation, the final clinical response rate is low (only 7%), and the migration rate of dendritic cells produced in vitro in lymph nodes is low (only 3-5%); What is more cumbersome is that the preparation of tumor vaccines based on dendritic cells needs to be made according to each individual patient, which is time-consuming, complicated and expensive. At present, there is still a lack of standard protocols for producing clinical-grade vaccines, so the quality is uncontrollable

Method used

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  • A mitochondria-targeted nanophotosensitive immune compound drug and its preparation method and application
  • A mitochondria-targeted nanophotosensitive immune compound drug and its preparation method and application
  • A mitochondria-targeted nanophotosensitive immune compound drug and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] A method for preparing a mitochondria-targeted nano photosensitive immune complex drug:

[0079] In this implementation, the phospholipid adopts distearoylphosphatidylethanolamine (hereinafter abbreviated as DSPE), and the lipophilic cationic group adopts the phenylphosphine group. Specifically, the lipophilic compound containing the phenylphosphine group adopts the 5-carboxypentyl Triphenylphosphine bromide, IR820 as photosensitizer, and CpG ODN 1826 as immune adjuvant;

[0080] In this implementation, the lipophilic cationic copolymer is first loaded on the nanocarrier to prepare the targeted nanocarrier (hereinafter referred to as GT), and then the immune adjuvant copolymer is loaded on the GT, and finally the photosensitizer is loaded to obtain the photosensitive immune system. compound drugs;

[0081] The following is the concrete operation of this embodiment:

[0082] Step 1: Synthesis of lipophilic cationic copolymer DSPE-PEG-TPP and DP-CpG copolymer;

[0083]...

Embodiment 2

[0100] Take 0.5 mL of the 0.5 mg / mL GT solution prepared in step 2 into a brown centrifuge tube, add 20 μL of the 0.22 mg / mL CpG ODN 1826 solution, and then place the mixed solution on a constant temperature shaker at a speed of 200 rpm. Reacted for 12 hours; after the reaction, the solution was transferred to a 10mL centrifuge tube, centrifuged at 15000rpm for 30 minutes, then washed three times with ultrapure water to remove unloaded CpG ODN 1826, and then Dilute pure water to 0.25mL, store at 4°C, and obtain a nanocomposite loaded with CpG ODN 1826 on nanographene oxide (hereinafter referred to as GT / CpG ODN nanocomposite);

[0101] In order to compare the encapsulation efficiency (EE) and drug loading rate (DLR) of the GT / CpG ODN nanocomposite prepared in this example and the GT / DP-CpG nanocomposite prepared in step 3 in Example 1, this example is obtained by The fluorescent probe FAM labeled CpG in the two nanocomposite solutions respectively, and the fluorescence intensi...

Embodiment 3

[0106] In this example, the photodynamic-photothermal properties of GT / DP-CpG / IR820 prepared in Example 1 of the present invention were tested, and the evaluation was mainly carried out by the following methods:

[0107] (1) Determination of singlet oxygen production rate in vitro:

[0108] This embodiment uses the green singlet oxygen probe (SOSG) to detect the singlet oxygen production rate of GT / DP-CpG / IR820 and photosensitizer IR820;

[0109] The detection principle is as follows: when there is no singlet oxygen, the electron transfer in the SOSG molecule quenches the fluorescence of the chromophore, while in the presence of singlet oxygen, SOSG forms an endoperoxide, resulting in a change in electron transfer, and the chromophore Fluorescence was recovered at 530nm. Therefore, the increase in the fluorescence intensity of SOSG at 530 nm directly reflects the production of singlet oxygen.

[0110] The specific operation of singlet oxygen yield measurement is as follows: ...

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Abstract

The invention provides a mitochondria-targeted nano-photosensitive immune compound drug and a preparation method and application thereof, which belong to the field of nano-medicine. The drug of the present invention includes water-soluble carbon-based nano-carriers, and mitochondria-targeted copolymers, immune adjuvant copolymers and photosensitizers respectively connected to the nano-carriers, thus constructing a mitochondria-targeted drug that combines phototherapy and immunotherapy The compound drug, which is used in in situ treatment of tumors, can efficiently target the subcellular organelles of in situ tumors—mitochondrion, and then generate singlet oxygen and photothermal effects. Singlet oxygen induces non-specific anti-tumor immune responses in the body, and in Under the action of immune adjuvants, the body's immune resistance against tumors can be further enhanced, and tumor-specific immunity can be generated to achieve the purpose of specifically inhibiting the development and metastasis of malignant tumors. The present invention has broad prospects in the field of treating tumors in situ or even metastatic tumors, and will become one of the important strategies for combined tumor sensitization therapy in the future.

Description

technical field [0001] The invention belongs to the field of nano-medicine, and in particular relates to a mitochondria-targeted nano-photosensitive immune compound drug and a preparation method and application thereof. Background technique [0002] As a kind of disease that seriously endangers human health, tumor is one of the important causes of global disease death. Malignant tumors develop rapidly and are prone to invasion or metastasis. At present, surgery, radiotherapy and chemotherapy are still the three conventional methods for treating tumors, but these methods have many shortcomings, such as damage to normal tissues, large systemic toxic and side effects, and high recurrence rate. Therefore, it is urgent to develop a new non-traditional treatment method to improve the therapeutic effect of cancer, reduce systemic side effects, and reduce the secondary recurrence rate. [0003] Tumor phototherapy is a method of precise targeted treatment of tumors, and it is a new...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/60A61K41/00A61K47/52A61K31/7088A61P35/00A61P35/04A61K39/39
CPCA61K31/7088A61K41/0052A61K41/0057A61K2039/55561B82Y5/00B82Y30/00B82Y40/00A61K2300/00
Inventor 吴春惠王莲慧田原官晓天刘秋月刘贻尧杨红曾红娟
Owner UNIV OF ELECTRONICS SCI & TECH OF CHINA
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