Anti-tumor magnetic drug-loading hybridized nanocapsules and preparation method thereof

A nanocapsule, anti-tumor technology, applied in the field of biomedical materials, can solve the problems of poor biocompatibility, drug release can not be well controlled, etc., to achieve good anti-tumor, good photothermal response behavior, inhibition of multiple The effect of drug resistance

Active Publication Date: 2019-04-26
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing nano-drug delivery system has poor biocompatibility, and the drug release cannot be well controlled. Therefore,

Method used

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  • Anti-tumor magnetic drug-loading hybridized nanocapsules and preparation method thereof
  • Anti-tumor magnetic drug-loading hybridized nanocapsules and preparation method thereof
  • Anti-tumor magnetic drug-loading hybridized nanocapsules and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1 Fe 3 o 4 Preparation of -OA

[0066] in N 2 Under protective conditions, add Fe(acac) to the three-necked bottle 3 , 1,2-hexadecanediol, OA and oleylamine, and finally add dibenzyl ether. Use a sand bath to heat, wait until the temperature rises slowly to 200°C, keep it warm for 2 hours, then slowly raise the temperature to 265°C, hold it for 1 hour, then cool to room temperature. The reactant in the three-neck flask was transferred to the Erlenmeyer flask for magnetic separation. After the magnetic separation was completed, the supernatant was poured off, and a small amount of ethanol was added to transfer the black precipitate to a centrifuge tube for centrifugation (3000 r / min, 5 min). The supernatant obtained by centrifugation was discarded, a small amount of n-hexane was added dropwise, and the black precipitate was transferred to a high-speed centrifuge tube for centrifugation (8000r / min, 10min). Pipette the upper layer suspension into a conical fl...

Embodiment 2

[0067] Example 2 TPGS-Cystamine-NH 2 and HO-PEG-Cystamine-NH 2 preparation of

[0068] Weigh TPGS, succinic anhydride and DMAP in a round-bottomed flask, dissolve with anhydrous dichloromethane, and place in N 2 The reaction was carried out under anhydrous and oxygen-free conditions for 24 hours. After the reaction was completed, the reaction solution was filtered, and the filtrate was collected. In a dialysis bag (cut-off Mw=1KDa), dialyze with 50% ethanol for 48h, then dialyze in deionized water for 48h, and freeze-dry to obtain the product, named TPGS-COOH; wherein TPGS, succinic anhydride and DMAP The mass ratio is 7.69:1:1.31.

[0069] The TPGS-COOH obtained above, EDC·HCl, NHS and cystamine hydrochloride were dissolved in deionized water in a round bottom flask, and the pH was adjusted to 6-7, and then reacted for 48 hours under magnetic stirring. After the reaction was completed, it was dialyzed in deionized water for three days (cut-off Mw=1KDa), and freeze-dried ...

Embodiment 3

[0072] Example 3 Preparation of Hep-TPGS-PEG-COOH

[0073] Sodium heparin, TPGS-Cystamine-NH 2 and HO-PEG-Cystamine-NH 2 Put it into a round bottom flask, then add EDC·HCl and NHS, mix well, then dissolve with deionized water, and adjust the pH of the solution to 6-7. After 48 hours of magnetic stirring reaction, the liquid was transferred to a dialysis bag (cut-off Mw=3500Da) and dialyzed with deionized water for 72 hours, and finally freeze-dried to obtain Hep-TPGS-PEG-OH. Among them, heparin sodium, TPGS-Cystamine-NH 2 , HO-PEG-Cystamine-NH 2 The mass ratio of , EDC·HCl and NHS is 4:1:1:2.24:1.36.

[0074] Put the Hep-TPGS-PEG-OH prepared above, succinic anhydride and DMAP in a round-bottomed branch bottle, dissolve with anhydrous DMF, react at room temperature under nitrogen protection for 24 hours, dialyze and freeze-dry to obtain PEG on the branched chain The heparin graft modification Hep-TPGS-PEG-COOH with -COOH at the end, wherein the mass ratio of Hep-TPGS-PEG-O...

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Abstract

The invention discloses anti-tumor magnetic drug-loading hybridized nanocapsules and a preparation method thereof. The preparation method comprises the following steps: firstly, preparing oleic acid coated magnetic ferroferric oxide nanoparticles (Fe3O4-OA); after modifying heparin sodium by TPGS (Tocopherol Polyethylene Glycol Succinate) and PEG (Polyethylene Glycol) through condensation reaction, carrying out an ultrasonic emulsification method to prepare Fe3O4-OA and adriamycin coated magnetic nanocapsules; then modifying the peripheries of the capsules with tumor cell-penetrating peptidesiRGD to provide a tumor cell targeting function; finally, treating through ammonium bicarbonate to form the magnetic drug-loading hybridized nanocapsules. The magnetic drug-loading hybridized nanocapsules prepared by the invention have strong targeting performance and have good stimulation response performance under the illumination of near infrared laser; carbon dioxide gas can be produced and high-selectivity rapid drug release of the nanocapsules on a tumor part is realized; meanwhile, the nanocapsules have good biocompatibility and high safety and also have certain magnetic response behaviors.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to an anti-tumor magnetic drug-loaded hybrid nanocapsule and a preparation method thereof. Background technique [0002] Malignant tumors seriously threaten human life and health. As a fatal and major malignant disease, due to its complex pathogenesis and disease progression, it also has the characteristics of easy transfer and high abnormal proliferation, which has caused more than one million deaths worldwide every year. The incidence of malignant tumors continues to rise, which greatly affects the healthy life of residents, and also brings a heavy economic burden to families and society. Therefore, tumor treatment is an urgent medical and social problem to be solved. Common treatments for tumors include surgery, radiation therapy, and chemotherapy. Among them, chemotherapy is a commonly used method in the clinical treatment of tumors today. Its treatme...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/02A61K47/42A61K47/36A61K47/22A61K47/04A61K31/704A61K41/00A61P35/00
CPCA61K9/5115A61K9/5146A61K9/5161A61K9/5169A61K31/704A61K41/0042A61P35/00A61K2300/00
Inventor 易强英康珂张宇佳马瑾
Owner SICHUAN UNIV
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