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作 者:Yueyue Fan Yuexin Cui Wenyan Hao Mengyu Chen Qianqian Liu Yuli Wang Meiyan Yang Zhiping Li Wei Gong Shiyong Song Yang Yang Chunsheng Gao
机构地区:[1]College of Pharmacy,Henan University,Kaifeng,475000,PR China [2]State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Institute of Pharmacology and Toxicology,Beijing,100850,PR China
出 处:《Bioactive Materials》2021年第12期4402-4414,共13页生物活性材料(英文)
基 金:We are grateful for the financial support from National Natural Science Foundation of China(Grant No.82073783).
摘 要:Nanosuspensions,as a new drug delivery system for insoluble drugs,are only composed of a drug and a small amount of stabilizer,which is dispersed in an aqueous solution with high drug-loading,small particle size,high dispersion,and large specific surface area.It can significantly improve the dissolution,bioavailability,and efficacy of insoluble drugs.In this study,paclitaxel nanosuspensions((PTX)NS)were prepared by an ultrasonic precipitation method,with the characteristics of simple preparation and easy repetition.With the help of a homologous targeting mechanism,a kind of glioma C6 cancer cell membrane(CCM)-coated(PTX)NS was developed and modified with DWSW peptide to obtain DWSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting.The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier(BBB)and selectively target tumor tissues.Cell uptake experiments and in vivo imaging confirmed that the uptake of DWSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased.Cytotoxicity test and in vivo anti-glioma studies showed that DWSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice.Finally,the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape.This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.
关 键 词:NANOSUSPENSIONS Cancer cell membrane Biomimetic drug-delivery systems GLIOMAS Blood-brain barrier Paclitaxel
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