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
