Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma

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...

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Main Authors: Yueyue Fan, Yuexin Cui, Wenyan Hao, Mengyu Chen, Qianqian Liu, Yuli Wang, Meiyan Yang, Zhiping Li, Wei Gong, Shiyong Song, Yang Yang, Chunsheng Gao
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2021-12-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X21001961
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author Yueyue Fan
Yuexin Cui
Wenyan Hao
Mengyu Chen
Qianqian Liu
Yuli Wang
Meiyan Yang
Zhiping Li
Wei Gong
Shiyong Song
Yang Yang
Chunsheng Gao
author_facet Yueyue Fan
Yuexin Cui
Wenyan Hao
Mengyu Chen
Qianqian Liu
Yuli Wang
Meiyan Yang
Zhiping Li
Wei Gong
Shiyong Song
Yang Yang
Chunsheng Gao
author_sort Yueyue Fan
collection DOAJ
description 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.
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spelling doaj.art-285fae7c269d4f64bc85a8eec71da7512024-04-16T21:53:04ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2021-12-0161244024414Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of gliomaYueyue Fan0Yuexin Cui1Wenyan Hao2Mengyu Chen3Qianqian Liu4Yuli Wang5Meiyan Yang6Zhiping Li7Wei Gong8Shiyong Song9Yang Yang10Chunsheng Gao11College of Pharmacy, Henan University, Kaifeng, 475000, PR China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaCollege of Pharmacy, Henan University, Kaifeng, 475000, PR China; Corresponding author.State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China; Corresponding author.College of Pharmacy, Henan University, Kaifeng, 475000, PR China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR ChinaNanosuspensions, 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.http://www.sciencedirect.com/science/article/pii/S2452199X21001961NanosuspensionsCancer cell membraneBiomimetic drug-delivery systemsGliomasBlood-brain barrierPaclitaxel
spellingShingle Yueyue Fan
Yuexin Cui
Wenyan Hao
Mengyu Chen
Qianqian Liu
Yuli Wang
Meiyan Yang
Zhiping Li
Wei Gong
Shiyong Song
Yang Yang
Chunsheng Gao
Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma
Bioactive Materials
Nanosuspensions
Cancer cell membrane
Biomimetic drug-delivery systems
Gliomas
Blood-brain barrier
Paclitaxel
title Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma
title_full Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma
title_fullStr Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma
title_full_unstemmed Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma
title_short Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma
title_sort carrier free highly drug loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma
topic Nanosuspensions
Cancer cell membrane
Biomimetic drug-delivery systems
Gliomas
Blood-brain barrier
Paclitaxel
url http://www.sciencedirect.com/science/article/pii/S2452199X21001961
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