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

doi:10.1021/acscentsci.6b00197

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

Radiology

Research output: Contribution to journal › Article › peer-review

91 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 language	English (US)
Pages (from-to)	802-811
Number of pages	10
Journal	ACS Central Science
Volume	2
Issue number	11
DOIs	https://doi.org/10.1021/acscentsci.6b00197
State	Published - Nov 23 2016

ASJC Scopus subject areas

Chemistry(all)
Chemical Engineering(all)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{feec557a29f349b88343aa18ad8b8a6b,

title = "PH-sensitive Pt nanocluster assembly overcomes cisplatin resistance and heterogeneous stemness of hepatocellular carcinoma",

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.",

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

note = "Funding Information: D.L. acknowledges financial support by the the National Key Research and Development Program of China (2016YFA0203600), the National Natural Science Foundation of China (51503180, 5161101036), {"}Thousand Talents Program{"} for Distinguished Young Scholars (588020∗G81501/048), and Fundamental Research Funds for the Central Universities (520002∗172210161). K.M.H. acknowledges financial support by the SingHealth Foundation and the National Medical Research Council, Singapore. T.H. acknowledges financial support by the Research Center Program of the Institute for Basic Science (IBS) in Korea (IBS-R006-D1). Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

year = "2016",

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doi = "10.1021/acscentsci.6b00197",

language = "English (US)",

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T1 - PH-sensitive Pt nanocluster assembly overcomes cisplatin resistance and heterogeneous stemness of hepatocellular carcinoma

AU - Xia, Hongping

AU - Li, Fangyuan

AU - Hu, Xi

AU - Park, Wooram

AU - Wang, Shuaifei

AU - Jang, Youngjin

AU - Du, Yang

AU - Baik, Seungmin

AU - Cho, Soojeong

AU - Kang, Taegyu

AU - Kim, Dong Hyun

AU - Ling, Daishun

AU - Hui, Kam Man

AU - Hyeon, Taeghwan

N1 - Funding Information: D.L. acknowledges financial support by the the National Key Research and Development Program of China (2016YFA0203600), the National Natural Science Foundation of China (51503180, 5161101036), "Thousand Talents Program" for Distinguished Young Scholars (588020∗G81501/048), and Fundamental Research Funds for the Central Universities (520002∗172210161). K.M.H. acknowledges financial support by the SingHealth Foundation and the National Medical Research Council, Singapore. T.H. acknowledges financial support by the Research Center Program of the Institute for Basic Science (IBS) in Korea (IBS-R006-D1). Publisher Copyright: © 2016 American Chemical Society.

PY - 2016/11/23

Y1 - 2016/11/23

N2 - 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.

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

Abstract

ASJC Scopus subject areas

UN SDGs

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