Bio-inspired protein-gold nanoconstruct with core-void-shell structure: Beyond a chemo drug carrier

Xiangyou Liu, Wei Wei, Shijiao Huang, Shrong Shi Lin, Xin Zhang, Chuanmao Zhang, Yuguang Du, Guanghui Ma, Mei Li, Stephen Mann, Ding Ma

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Chemotherapy has been widely used in clinical practice for cancer treatment. A major challenge for a successful chemotherapy is to potentiate the anticancer activity, whilst reducing the severe side effects. In this context, we design a bio-inspired protein-gold nanoconstruct (denoted as AFt-Au hereafter) with a core-void-shell structure which exhibits a high selectivity towards carcinoma cells. Anticancer drug 5-fluorouracil (5-FU) can be sequestered into the void space of the construct to produce an integrated nanoscale hybrid AFt-AuFU that exhibits an increased cellular uptake of 5-FU. More importantly, AFt-Au, serving as a bio-nano-chemosensitizer, renders carcinoma cells more susceptible to 5-FU by cell-cycle regulation, and thus, leads to a dramatic decrease of the IC50 value (i.e. the drug concentration required to kill 50% of the cell population) of 5-FU in HepG2 cells from 138.3 μM to 9.2 μM. Besides HepG2 cells, a remarkably enhanced anticancer efficacy and potentially reduced side effects are also achieved in other cell lines. Our further work reveals that the drug 5-FU is internalized into cells with AFt-Au primarily via receptor-mediated endocytosis (RME). After internalization, AFt-AuFU colocalizes with lysosomes which trigger the release of 5-FU under acidic conditions. Overall, our approach provides a novel procedure in nanoscience that promises an optimal chemotherapeutic outcome.

Original languageEnglish (US)
Pages (from-to)3136-3143
Number of pages8
JournalJournal of Materials Chemistry B
Volume1
Issue number25
DOIs
StatePublished - Jul 7 2013

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All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

Cite this

Liu, X., Wei, W., Huang, S., Lin, S. S., Zhang, X., Zhang, C., Du, Y., Ma, G., Li, M., Mann, S., & Ma, D. (2013). Bio-inspired protein-gold nanoconstruct with core-void-shell structure: Beyond a chemo drug carrier. Journal of Materials Chemistry B, 1(25), 3136-3143. https://doi.org/10.1039/c3tb20081g