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Tumor microenvironment response type nanoparticle based on biomimetic engineering as well as preparation method and application thereof

A technology of tumor microenvironment and bionic engineering, which is applied in the field of tumor microenvironment-responsive nanoparticles and its preparation, can solve the problems that photothermal efficacy cannot be fully exerted, chelates cannot exist stably, etc., and achieve a wide range of acquisition channels Effect

Inactive Publication Date: 2021-04-06
CHONGQING MEDICAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the exogenous or endogenous acidic tumor microenvironment (including endosomes with a pH of 5.5-6.0 and lysosomes with a pH of 4.5-5.0, etc.) will promote the chelation of iron ions and tannic acid formation The chelate exhibits a pH-dependent decomposition behavior after reaching the tumor site, resulting in the inability of the chelate to exist stably in the tumor site, and its photothermal effect cannot be fully exerted

Method used

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  • Tumor microenvironment response type nanoparticle based on biomimetic engineering as well as preparation method and application thereof
  • Tumor microenvironment response type nanoparticle based on biomimetic engineering as well as preparation method and application thereof
  • Tumor microenvironment response type nanoparticle based on biomimetic engineering as well as preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Embodiment 1: the preparation of PFTNPs

[0065] First, PpIX (protoporphyrin, 10 mg) was dissolved in 2 mL of methanol to obtain a PpIX methanol solution. Quickly add 200 μl PpIX methanol solution to deionized water (amount of 5-30ml, 20ml is used in this example), and under continuous ultrasonic treatment (ultrasonic power is 50-100W, 100W is used in this example), add 40 μl TA solution (40mg / mL) and 40μl FeCl 3 .6H 2 O (10 mg / mL), nanoparticles dispersed in the aqueous phase were obtained. Next, the nanoparticles were washed with deionized water and centrifuged at 10,000 rpm for 10 min, and then the nanoparticles were taken and neutralized with NaOH to obtain PFTNPs (ie, PpIX@FeIII / TA).

Embodiment 2

[0066] Embodiment 2: Preparation of MPFTNPs

[0067] 1. Synthesis of PFTNPs

[0068] Refer to Example 1 for the preparation process.

[0069] 2. Cancer Cell Culture

[0070] MDA-MB-231 human breast cancer cells were incubated at 37°C with 5% CO 2 The culture medium was high-glucose DMEM medium supplemented with 10% FBS (v / v) and 1% penicillin-streptomycin (v / v).

[0071] 3. Extraction of Cancer Cell Membranes

[0072] MDA-MB-231 cell membranes were extracted with a membrane protein extraction kit according to the instructions provided by Beyotime Biotechnology Company. Simply put, the collected 1×10 8 The cells were resuspended in 3ml membrane protein extract solution and 1mMPMSF was added. The cells were gently and fully suspended, and then incubated in an ice bath for 15 minutes. The MDA-MB-231 cell suspension was frozen at -80 °C and then thawed three times. The obtained suspension was centrifuged at 700 g for 10 min, and the supernatant was centrifuged at 4° C. (14...

experiment example 1

[0076] Experimental example 1: Cellular uptake performance of MPFTNPs

[0077] MDA-MB-231 cells, HepG2 cells and PANC-1 cells were seeded in glass confocal culture dishes overnight. The MPFTNP solution with a concentration of 40 μg / mL was added, the cells were incubated for 1 h, and then the cancer cells were washed three times with fresh DMEM medium, stained with DAPI for 10 min, and the cell uptake performance of MPFTNPs was observed under CLSM (LSM710, Carl-Zeiss, Germany). Experimental results such as Figure 6 As shown, it is proved that MPFTNP has strong targeting to MDA-MB-231 cells.

[0078] The cell uptake behavior was detected by flow cytometry (BD-FACSVantage SE, USA). Similar to the CLSM test method, MDA-MB-231 cells, PANC-1 cells and HepG2 cells were seeded in 6-well plates and incubated with MPFTNPs at a dose of 40 mg / mL. After culturing for 1 h, the cells were washed with DMEM medium and analyzed by flow cytometry. Experimental results such as Figure 7 As ...

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Abstract

The invention relates to the technical field of biomedicine, in particular to a tumor microenvironment response type nanoparticle based on biomimetic engineering as well as a preparation method and application of the tumor microenvironment response type nanoparticle. The nanoparticle comprises a chelate shell layer formed by tannic acid and ferric ions, a cancer cell membrane is adsorbed outside the chelate shell layer, and a photosensitizer is entrapped in the chelate shell layer. The tumor microenvironment stability of the nanoparticles is improved through cancer cell membrane modification, and the nanoparticles also have tumor targeting, so that the imaging and tumor treatment effects of the nanoparticles are improved. The nanoparticles can be used as T1 weighted nuclear magnetic resonance, photoacoustic imaging and photo-thermal imaging contrast agents, can be used as photodynamic therapy drugs and photo-thermal therapy drugs, and can be widely applied to cancer treatment and diagnosis.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a tumor microenvironment-responsive nanoparticle based on bionic engineering and its preparation method and application. Background technique [0002] Photothermal therapy (PTT), a promising alternative to traditional radiotherapy and chemotherapy, is also considered as a tumor-specific treatment modality with high spatiotemporal selectivity and low toxicity. Photothermal therapy specifically refers to the conversion of light energy into thermal energy by photothermal conductive agents, and subsequently increases the temperature of the tumor site to induce cancer cell death. [0003] The material formed by the chelation of metal ions and tannic acid is a new type of organic-inorganic hybrid material, which has the advantages of high photothermal conversion efficiency, strong photothermal stability and good biocompatibility. Among them, nanoparticles prepared from chelates fo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K9/51A61K47/46A61P35/00A61K49/22A61K49/10A61K49/18
CPCA61K41/0052A61K41/0071A61K9/5176A61P35/00A61K49/225A61K49/106A61K49/1845A61K2300/00
Inventor 乔斌王志刚罗远利曹进冉海涛李攀任建丽郝兰
Owner CHONGQING MEDICAL UNIVERSITY
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