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Oxygen-carrying and drug-loading self-assembled nano-drug with molecular targeting/sonodynamic therapy (SDT) and preparation method thereof

A technology of sonodynamic therapy and nano-medicine, which is applied in the field of biomedicine, can solve problems such as limiting the curative effect of SDT, and achieve the effect of improving the therapeutic effect, accelerating the release, and improving the hypoxic state of the tumor

Active Publication Date: 2021-03-05
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The tumor microenvironment is in a hypoxic state, because SDT is an oxygen-consuming process, so this hypoxic environment limits the efficacy of SDT, and is also related to drug resistance

Method used

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  • Oxygen-carrying and drug-loading self-assembled nano-drug with molecular targeting/sonodynamic therapy (SDT) and preparation method thereof
  • Oxygen-carrying and drug-loading self-assembled nano-drug with molecular targeting/sonodynamic therapy (SDT) and preparation method thereof
  • Oxygen-carrying and drug-loading self-assembled nano-drug with molecular targeting/sonodynamic therapy (SDT) and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045]Disperse 1 g of Cs in 50 mL of DMF, add 2 g of 4-bromophthalic anhydride, stir at 125 °C under nitrogen protection until the solution is clear, pour the hot filtrate into 500 mL of ice water, a white solid precipitates out, and control the temperature for Centrifuge at -8°C at 5000 r / min for 5 min, and the obtained solid is chitosan substituted with brominated phthalic anhydride. Weigh 1 g of the above product and disperse it in 50 mL of N-methylpyrrolidone, heat it in an oil bath at 50 °C until it is completely dissolved, add 1.66 g of sodium azide to it, and continue the reaction for 24 hours under nitrogen protection. The reaction solution was poured into 100 mL of ethanol to precipitate solids, centrifuged at 12,000 r / min for 5 min, the precipitate was washed with water and acetone, and then vacuum-dried to obtain azide-substituted chitosan. Weigh 1 g of azide-substituted chitosan and disperse it in 30 mL of DMSO, heat and stir for 20-30 min until completely dissolve...

Embodiment 2

[0047] Disperse 10 mg CE in 1 mL DMSO, 1 mg HP was dissolved in 0.25 mL DMSO, 0.25 mL PFOB was dissolved in 0.25 mL chloroform, and the HP solution and the PFOB solution were added dropwise to the CE solution in turn. Magnetically stirred for 24 h, prepared a small beaker with 20 mL of double distilled water, and slowly added the above solution dropwise into the double distilled water under magnetic stirring, magnetically stirred for 24 h at room temperature and protected from light, and placed the reaction solution in a place with a molecular weight cut off of 8000 ~14,000 dialysis bags were dialyzed in deionized water for 24 h, and the water was changed every 6 h. The dialysate was dried by a freeze dryer to obtain Er-modified Cs nanoparticles CEPH loaded with PFOB and HP, which were stored at -20°C.

[0048] The prepared CEPH was dispersed to a certain concentration with DMSO, and the UV absorption was measured with a UV spectrophotometer, from figure 1 It can be seen that...

Embodiment 3

[0050] Take 10 mg CE and disperse it in 1 mL DMSO, then add the HP DMSO solution (1 mg HP dissolved in 0.25 mL DMSO) dropwise to the above solution, stir magnetically for 24 h under dark conditions, and prepare 20 mL In a small beaker of double-distilled water, under magnetic stirring, slowly add the above solution dropwise into double-distilled water, stir magnetically for 24 hours at room temperature and avoid light, and transfer the reaction solution to a dialysis bag with a molecular weight cut-off of 8000-14000 in deionized water Dialysis was performed for 24 h, and the water was changed every 6 h. The dialysate was dried by a freeze dryer to obtain Er-modified Cs nanoparticles (CEH) loaded with HP.

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Abstract

The invention discloses an oxygen-carrying and drug-loading self-assembled nano-drug with molecular targeting / sonodynamic therapy (SDT) and a preparation method thereof. According to the nano-drug, erlotinib-modified chitosan (CE) is used as a carrier, then hematoporphyrin (HP) and perfluorooctane bromide (PFOB) are loaded, and CE / PFOB / HP self-assembled nanoparticles (CEPH) are prepared through self-assembly. As a sound sensitizer, the HP can play a role in SDT; and the PFOB carries oxygen and can improve the microenvironment of tumor relative to hypoxia, enhance the SDT effect and overcome the drug resistance of tumor cells to a chemotherapeutic drug Er (erlotinib) under the hypoxia condition. According to the nano-drug, molecular targeted therapy and SDT are combined, the PFOB is used for reversing drug resistance, and tumor cell proliferation can be inhibited to the maximum extent through cooperation of molecular targeted therapy, SDT and PFOB.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to an oxygen-carrying drug-loaded self-assembled nano-medicine with molecular targeting and sonodynamic therapy and a preparation method thereof. Background technique [0002] The incidence of lung cancer has been increasing year by year, and it has become one of the most lethal tumors. Among them, non-small cell lung cancer (NSCLC) accounts for 80-85% of the total number of lung cancers. With traditional treatment methods such as surgery, radiotherapy and chemotherapy, the prognosis is very poor, and the five-year survival period is very low. Molecular targeted drugs represented by tyrosine kinase inhibitors such as erlotinib have been widely used in clinical practice due to their remarkable effects in the treatment of lung cancer, few side effects, and significantly prolonged survival. However, some lung cancer patients develop drug resistance during the treatment with molecularly target...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K47/69A61P35/00B82Y5/00B82Y30/00B82Y40/00A61K31/02A61K31/517
CPCA61K31/02A61K31/517A61K41/0033A61K47/6939A61P35/00B82Y5/00B82Y30/00B82Y40/00A61K2300/00
Inventor 高瑜张培霞张露陈海军
Owner FUZHOU UNIV
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