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.
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China; Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Center Singapore, 169610, Singapore.
authors.forename: Hongping
authors.initials: H
authors.lastname: Xia
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Li
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University , Hangzhou 310058, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Radiology, Northwestern University and Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, United States.
authors.forename: Wooram
authors.initials: W
authors.lastname: Park
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University , Hangzhou 310058, China.
authors.forename: Shuaifei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Korea; School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Korea.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University , Hangzhou 310058, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Du
authors.affiliation: Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Korea; School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Korea.
authors.forename: Seungmin
authors.initials: S
authors.lastname: Baik
authors.affiliation: Department of Radiology, Northwestern University and Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, United States.
authors.forename: Soojeong
authors.initials: S
authors.lastname: Cho
authors.affiliation: Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Korea; School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Korea.
authors.forename: Taegyu
authors.initials: T
authors.lastname: Kang
authors.affiliation: Department of Radiology, Northwestern University and Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, United States; Department of Radiology, Northwestern University and Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, United States.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China.
authors.forename: Daishun
authors.initials: D
authors.lastname: Ling
authors.affiliation: Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Center Singapore, 169610, Singapore; Cancer and Stem Cell Biology Program, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Kam Man
authors.initials: KM
authors.lastname: Hui
authors.affiliation: Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Korea; School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Korea.
authors.forename: Taeghwan
authors.initials: T
authors.lastname: Hyeon