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• W1828772531 abstract "// He Wang 1,2,* , Henghui Yin 3,* , Fengjiao Yan 4 , Mingna Sun 2 , Lingran Du 2 , Wei Peng 2 , Qiuli Li 2 , Yinghong Feng 5 and Yi Zhou 2 1 Department of Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China 2 The College of Pharmaceutics Science, Guangzhou Medical University, Guangzhou, Guangdong, China 3 Center of Breast Disease, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China 4 Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China 5 Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA * These authors contributed equally to this work Correspondence: Yi Zhou, email: // Keywords : Polyrotaxanes, Functional DOX nanoparticles, Multidrug resistance, Mitochondrial signaling pathway Received : October 30, 2014 Accepted : December 25, 2014 Published : December 30, 2014 Abstract Resistance to treatment with anticancer drugs is a significant obstacle and a fundamental cause of therapeutic failure in cancer therapy. Functional doxorubicin (DOX) nanoparticles for targeted delivery of the classical cytotoxic anticancer drug DOX to tumor cells, using folate-terminated polyrotaxanes along with dequalinium, have been developed and proven to overcome this resistance due to specific molecular features, including a size of approximately 101 nm, a zeta potential of 3.25 mV and drug-loading content of 18%. Compared with free DOX, DOX hydrochloride, DOX nanoparticles, and targeted DOX nanoparticles, the functional DOX nanoparticles exhibited the strongest anticancer efficacy in vitro and in the drug-resistant MCF-7/Adr (DOX) xenograft tumor model. More specifically, the nanoparticles significantly increased the intracellular uptake of DOX, selectively accumulating in mitochondria and the endoplasmic reticulum after treatment, with release of cytochrome C as a result. Furthermore, the caspase-9 and caspase-3 cascade was activated by the functional DOX nanoparticles through upregulation of the pro-apoptotic proteins Bax and Bid and suppression of the antiapoptotic protein Bcl-2, thereby enhancing apoptosis by acting on the mitochondrial signaling pathways. In conclusion, functional DOX nanoparticles may provide a strategy for increasing the solubility of DOX and overcoming multidrug-resistant cancers." @default.
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• W1828772531 date "2014-12-30" @default.
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• W1828772531 title "Folate-mediated mitochondrial targeting with doxorubicin-polyrotaxane nanoparticles overcomes multidrug resistance" @default.
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• W1828772531 doi "https://doi.org/10.18632/oncotarget.3090" @default.
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