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Albumin nano drug delivery system with anti-tumor metastasis and targeting functions and preparation method of albumin nano drug delivery system

An anti-tumor metastasis, albumin nano-technology, applied in the field of albumin nano-drug delivery system and its preparation, can solve the problems of chemotherapeutic drug encapsulation efficiency, low drug loading, short circulation half-life, easy to be cleared, and difficulty in inhibiting metastasis , to reduce the formation of lung metastases, improve the tumor microenvironment, and prolong the survival of animals

Inactive Publication Date: 2021-03-30
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0002] The prior art discloses that cancer is one of the biggest killers of human health at present. Triple-negative breast cancer (TNBC) accounts for about 10%-20% of current breast cancers, and its surface estrogen receptor, progesterone receptor and HER2 expression are all It is negative and is the only type of breast cancer that has no approved targeted therapy; in addition, it also has problems such as high interstitial pressure, high invasiveness, and easy recurrence, and the prognosis is poor
Traditional treatment, including surgery, radiotherapy and chemotherapy, can treat tumors before the cancer cells spread and achieve good results, but there is no good method for tumor metastasis and recurrence, resulting in high mortality of patients
[0003] Traditional chemotherapeutic drugs usually have problems of poor solubility, short half-life in vivo circulation, easy to be cleared, and difficult to accumulate in the tumor site. The current countermeasures mostly use nanotherapy, which can not only effectively entrap hydrophobic drugs, but also take advantage of the penetration of tumor sites. and retention effect (EPR effect) to achieve high accumulation effect
However, nanotherapy also has certain limitations, such as the low encapsulation efficiency and drug loading capacity of chemotherapeutic drugs, and it is easy to be cleared by the monocyte phagocytic system in the process of circulation in the body, etc.
At the same time, although simple delivery of chemotherapeutic drugs using nanosystems can inhibit the growth of tumors in situ, it is difficult to inhibit metastasis and even promote metastasis.

Method used

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  • Albumin nano drug delivery system with anti-tumor metastasis and targeting functions and preparation method of albumin nano drug delivery system
  • Albumin nano drug delivery system with anti-tumor metastasis and targeting functions and preparation method of albumin nano drug delivery system
  • Albumin nano drug delivery system with anti-tumor metastasis and targeting functions and preparation method of albumin nano drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1: Preparation, Characterization and Cytotoxicity of Materials and Nanoformulations

[0059] The biguanide group is connected to albumin by chemical reaction, 1H-pyrazole-1-carboxamidine hydrochloride (AH) is self-condensed to form biguanide hydrochloride (NH), and 133 mg of HSA is mixed with 35 mg of AH and NH Dissolve in 2 mL triple distilled water, then add 30 μL N,N-diisopropylethylamine (DIEA), stir at room temperature for 24 hours, use triple distilled water to dialyze for two days, freeze-dry to obtain HSA-AH and HSA-NH, use ultraviolet spectroscopic A photometer detects the progress of the reaction;

[0060] The nano drug delivery system was prepared by emulsification-solvent evaporation method. Weigh 20mg of PLGA, dissolve in 1ml of 0.5mg / ml PTX dichloromethane solution, and vortex to dissolve. Add 2ml of 1% sodium cholate solution, and ultrasonicate for 2.5min in an ice-water bath. The working time and interval are both 2s, and the ultrasonic power i...

Embodiment 2

[0062] Example 2: Cell uptake and pathway investigation of nano-preparations

[0063] In order to prove the importance of albumin and biguanide groups in the outer layer of nanoparticles to the uptake by cells, 4T1 breast cancer cells and Raw264.7 macrophages were selected to investigate their uptake of various nano-preparations. Each nanoparticle is fluorescently labeled by encapsulating coumarin-6 by emulsification-solvent evaporation method. After 24 hours in the 96-well plate of 4T1 and Raw264.7 cell species, aspirate the medium, add nanoparticles according to the pre-set concentration gradient table, absorb the nanoparticles after 2 hours, wash with phosphate buffer saline (PBS), and add 4% polymer After formaldehyde fixation for 15 minutes and cell nuclear dye (Hoechst reagent) in the dark for 8 minutes, the high-content analysis system was used to investigate the qualitative and quantitative results of cell uptake;

[0064] In order to prove the mechanism of nano-prepa...

Embodiment 3

[0066] Embodiment 3: the impact of nano preparation on tumor EMT effect

[0067] According to the literature and previous experimental results in the laboratory, metformin has the ability to inhibit the epithelial-mesenchymal transition (EMT) of cancer cells, and thus can inhibit the metastasis of cancer. In order to investigate the effects of several nano-preparations on the EMT effect of 4T1 tumors, after 24 hours in a 6-well plate of 4T1 cells, the dosage concentration of paclitaxel equivalent 150ng / ml was added to the free drug, PLGANP, HSANP, HSA-AH, HSA-NHNP Several preparations were incubated in the incubator for 24 hours, the supernatant was sucked off, washed 3 times with PBS, and the 6-well plate was placed on ice, and 250 μL of RIPA lysate was added to each well to lyse for 30 minutes, and the cells were scraped off with a cell scraper. Add the cell debris and lysate into a 1.5mL centrifuge tube, and centrifuge at 4°C and 12000rpm / min for 10min. Transfer the supern...

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Abstract

The invention belongs to the field of pharmaceutical preparations, and relates to an albumin nano drug delivery system with anti-tumor metastasis and targeting functions and a preparation method of the albumin nano drug delivery system, and the albumin nano drug delivery system comprises a chemotherapeutic drug and a nano drug delivery system for targeting a tumor, improving chemotherapeutic effect and inhibiting metastasis. According to the invention, a biguanide group is combined to albumin, the albumin is used for coating a biodegradable high polymer material polylactic acid-glycolic acid copolymer (PLGA), and chemotherapeutic drug paclitaxel is coated by an emulsified-solvent evaporation method, so that a multifunctional targeting drug-loading nano system is constructed. The delivery system is accumulated at an in-vivo tumor part and is preferentially ingested by tumor cells, the tumor cells are killed by combining paclitaxel and biguanide albumin, tumor metastasis is inhibited, the lifetime is prolonged, and meanwhile, the delivery system has good biological safety and has broad prospects in the aspects of treating triple-negative breast cancer and metastasis thereof.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an albumin nano drug delivery system with anti-tumor metastasis and targeting functions and a preparation method thereof. The albumin nano drug delivery system includes a chemotherapeutic drug and a tumor targeting and Nano drug delivery system to improve chemotherapy efficacy and inhibit metastasis. Background technique [0002] The prior art discloses that cancer is one of the biggest killers of human health at present. Triple-negative breast cancer (TNBC) accounts for about 10%-20% of current breast cancers, and its surface estrogen receptor, progesterone receptor and HER2 expression are all It is negative, and it is the only type of breast cancer that has no approved targeted therapy; in addition, it also has problems such as high interstitial pressure, high invasiveness, and easy recurrence, and the prognosis is poor. Traditional treatments, including surgery, radio...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/34A61K47/42A61K31/337A61P35/00
CPCA61K9/5153A61K9/5169A61K31/337A61P35/00
Inventor 陈钧王家豪
Owner FUDAN UNIV
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