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pH-sensitive Pt nanocluster assembly overcomes cisplatin resistance and heterogeneous stemness of hepatocellular carcinoma

Cited 48 time in Web of Science Cited 51 time in Scopus
Authors
Xia, Hongping; Li, Fangyuan; Hu, Xi; Park, Wooram; Wang, Shuaifei; Jang, Youngjin; Du, Yang; Baik, Seungmin; Cho, Soojeong; Kang, Taegyu; Kim, Dong-Hyun; Ling, Daishun; Hui, Kam Man; Hyeon, Taeghwan
Issue Date
2016-11
Citation
ACS Central Science, Vol.2 No.11, pp.802-811
Abstract
Response rates to conventional chemotherapeutics remain unsatisfactory for hepatocellular carcinoma (HCC) due to the high rates of chemoresistance and recurrence. Tumor-initiating cancer stem-like cells (CSLCs) are refractory to chemotherapy, and their enrichment leads to subsequent development of chemoresistance and recurrence. To overcome the chemoresistance and stemness in HCC, we synthesized a Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters incorporating a pH-sensitive polymer and HCC-targeting peptide. Pt-NA is latent in peripheral blood, readily targets disseminated HCC CSLCs, and disassembles into small Pt nanoclusters in acidic subcellular compartments, eventually inducing damage to DNA. Furthermore, treatment with Pt-NA downregulates a multitude of genes that are vital for the proliferation of HCC. Importantly, CD24+ side population (SP) CSLCs that are resistant to cisplatin are sensitive to Pt-NA, demonstrating the immense potential of Pt-NA for treating chemoresistant HCC.
ISSN
2374-7951
URI
http://hdl.handle.net/10371/165987
DOI
https://doi.org/10.1021/acscentsci.6b00197
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College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Journal Papers (저널논문_화학생물공학부)
College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Chemical Convergence for Energy and Environment (에너지환경 화학융합기술전공)Journal Papers (저널논문_에너지환경 화학융합기술전공)
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