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

doi:10.1039/C3TB20081G

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

Xiangyou Liu,‡^ae Wei Wei,‡^b Shijiao Huang,^c Shrong-Shi Lin,^a Xin Zhang,^d Chuanmao Zhang,^c Yuguang Du,^e Guanghui Ma,^b Mei Li,^f Stephen Mann^f and Ding Ma*^a

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* Corresponding authors

^a Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
E-mail: dma@pku.edu.cn

^b National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China

^c The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China

^d Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

^e Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China

^f Center for Organized Matter Chemistry, School of chemistry, University of Bristol, Bristol, UK

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 drug5-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.

Journal of Materials Chemistry B

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

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

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