Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 3, Issue 48, Pages 9383-9396Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5tb00328h
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Funding
- National Natural Science Foundation of China [31270019, 51203085]
- Guangdong Natural Science Funds for Distinguished Young Scholar [2014A030306036]
- China Postdoctoral Science Foundation [2015M580109]
- Scientific and Technological Innovation Bureau of Nanshan District [KC2014JSCX0023A]
- Science, Technology & Innovation Commission of Shenzhen Municipality [JCYJ20150430163009479, JCYJ20150529164918738, CYZZ 20130320110255352]
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Poly(lactide-co-glycolide) (PLGA)-based particles have been widely used as carriers of various kinds of drugs, which are sequestered by the cell membrane and degraded through endo-lysosome and auto-lysosomal pathways. Lysosome is the destination of endocytosis and autophagy, which is also an organelle for the cell to execute death. Here, we show that chloroquine (CQ) and ciprofloxacin (CPX) (LMP inducer reagents)-loaded PLGA hollow microspheres (HMs) could be delivered by passive targeting into endo-lysosome and auto-lysosome. Co-loading with NaHCO3 accelerates the release of CQ and CPX in the acid environment of endo-lysosome and auto-lysosome. Subsequently, the released CQ and CPX induce lysosomal membrane permeabilization (LMP), which leads to cancer cell death in three different manners: apoptosis, autophagic cell death and apoptosis with autophagosome. Moreover, we use rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR), to induce autophagy and inhibit cell growth. Rapamycin-NaHCO3-loaded HMs combined CQ-NaHCO3-loaded HMs could efficiently induce cancer cell death through apoptosis with autophagosome both in vitro and in vivo.
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