Intracellular fate of nanoparticles with polydopamine surface engineering and a novel strategy for exocytosis-inhibiting, lysosome impairment-based cancer therapy

Li Ding, Xianbing Zhu, Yiling Wang, Bingyang Shi, Xiang Ling, Houjie Chen, Wenhao Nan, Austin Barrett, Zilei Guo, Wei Tao*, Jun Wu, Xiaojun Shi

*Corresponding author for this work

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6790-6801
Number of pages12
JournalNano Letters
Volume17
Issue number11
DOIs
Publication statusPublished - 8 Nov 2017
Externally publishedYes

Keywords

  • exocytosis-inhibiting
  • intracellular fate
  • lysosome targeting
  • Nanoparticle
  • polydopamine coating and shedding

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