pH-Sensitive Pt Nanocluster Assembly Overcomes Cisplatin Resistance and Heterogeneous Stemness of Hepatocellular Carcinoma | Zendy

Hongping Xia | Zendy; Fangyuan Li | Zendy; Xi Hu | Zendy; Wooram Park | Zendy; Shuaifei Wang | Zendy; Young Jin Jang | Zendy; Yang Du | Zendy; Seungmin Baik | Zendy; Soojeong Cho | Zendy; Taegyu Kang | Zendy; DongHyun Kim | Zendy; Daishun Ling | Zendy; Kam M. Hui | Zendy; Taeghwan Hyeon | Zendy

Open Access

pH-Sensitive Pt Nanocluster Assembly Overcomes Cisplatin Resistance and Heterogeneous Stemness of Hepatocellular Carcinoma

Author(s) -

Hongping Xia,

Fangyuan Li,

Xi Hu,

Wooram Park,

Shuaifei Wang,

Young Jin Jang,

Yang Du,

Seungmin Baik,

Soojeong Cho,

Taegyu Kang,

DongHyun Kim,

Daishun Ling,

Kam M. Hui,

Taeghwan Hyeon

Publication year - 2016

Publication title -

acs central science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 4.893

H-Index - 76

eISSN - 2374-7951

pISSN - 2374-7943

DOI - 10.1021/acscentsci.6b00197

Subject(s) - hepatocellular carcinoma , cisplatin , nanoclusters , cancer research , cancer stem cell , population , chemistry , biology , cancer , medicine , chemotherapy , organic chemistry , environmental health

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.

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