期刊
NANO LETTERS
卷 17, 期 11, 页码 6790-6801出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.7b03021
关键词
Nanoparticle; polydopamine coating and shedding; intracellular fate; lysosome targeting; exocytosis-inhibiting
类别
资金
- Thousand Talents Plan for Young Professionals
- Science and Technology Planning Project of Guangdong Province [2016A010103015]
- Guangdong Innovative and Entrepreneurial Research Team Program [2013S086, 2016ZT06S029]
- Science and Technology Program of Guangzhou [201707010094]
- Natural Science Foundation of Guangdong Province [2016A030310023]
- China Postdoctoral Science Foundation [2016M600676]
- Tsinghua Scholarship for Overseas Graduate Studies [2013159]
Polydopamine (PDA) coating as a bioinspired strategy for nanoparticles (NPs) has been extensively applied in cancer theranostics. However, a cellular-level understanding of nano-biointeraction of these PDA-coated NPs (PDNPs), which drives the fate of them and acts as a critical step to determine their efficacy, still remains unknown. Herein, we utilized the representative mesoporous silica NPs (MSNs) to be coated with PDA and study their nano-bioactivities in cancer cells. HeLa cell line was utilized as a model in this study. The PDNPs were discovered to be internalized through three specific pathways, that is, Caveolae-, Arf6-dependent endocytosis, and Rab34-mediated macropinocytosis (55%, 20% and 37% of uptake inhibition by nystatin, Arf6 knockdown, and rottlerin, respectively). Autophagy-mediated accumulation of PDNPs in lysosomes was observed and the formed PDA shells shedded in the lysosomes. Almost 40% of the NPs were transported out of cells via Rab8/10- and Rab3/26-mediated exocytosis pathways at our tested level. On the basis of these results, a novel combined cancer treatment strategy was further proposed using drug-loaded MSNs-PDA by (i) utilizing naturally intracellular mechanism-controlled PDA shedding for organelle-targeted release of drugs in lysosomes to generate lysosome impairment and (ii) blocking the demonstrated exocytosis pathways for enhanced therapeutic efficacy.
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