pH-Sensitive Pt Nanocluster Assembly Overcomes Cisplatin Resistance and Heterogeneous Stemness of Hepatocellular Carcinoma
| Autor: | Daishun Ling, Yang Du, Fangyuan Li, Wooram Park, Xi Hu, Youngjin Jang, Kam M. Hui, Seungmin Baik, Soojeong Cho, Taegyu Kang, Hongping Xia, Taeghwan Hyeon, Dong-Hyun Kim, Shuaifei Wang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
General Chemical Engineering
medicine.medical_treatment 02 engineering and technology 010402 general chemistry 01 natural sciences Nanoclusters lcsh:Chemistry chemistry.chemical_compound Side population medicine Cisplatin Chemotherapy CD24 Cancer General Chemistry 021001 nanoscience & nanotechnology medicine.disease Virology digestive system diseases 0104 chemical sciences lcsh:QD1-999 chemistry Hepatocellular carcinoma Cancer research 0210 nano-technology DNA Research Article medicine.drug |
| Zdroj: | ACS Central Science, Vol 2, Iss 11, Pp 802-811 (2016) ACS Central Science |
| ISSN: | 2374-7951 2374-7943 |
| Popis: | 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. A Pt-nanocluster assembly, by clustering extremely small-sized Pt nanoclusters with pH-sensitive polymers and a liver cancer cell targeting peptide, is demonstrated to effectively overcome the chemoresistance and stemness of hepatocellular carcinoma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|