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

Hongping Xia, Fangyuan Li, Xi Hu, Wooram Park, Shuaifei Wang, Youngjin Jang, Yang Du, Seungmin Baik, Soojeong Cho, Taegyu Kang, Dong Hyun Kim, Daishun Ling*, Kam Man Hui, Taeghwan Hyeon

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)802-811
Number of pages10
JournalACS Central Science
Volume2
Issue number11
DOIs
StatePublished - Nov 23 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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    Xia, H., Li, F., Hu, X., Park, W., Wang, S., Jang, Y., Du, Y., Baik, S., Cho, S., Kang, T., Kim, D. H., Ling, D., Hui, K. M., & Hyeon, T. (2016). PH-sensitive Pt nanocluster assembly overcomes cisplatin resistance and heterogeneous stemness of hepatocellular carcinoma. ACS Central Science, 2(11), 802-811. https://doi.org/10.1021/acscentsci.6b00197