P-selectin-targeted Polyguluronate sulfate-copper peroxide Nanomicelles for Chemodynamic therapy of breast Cancer

Abstract

The exploration of efficient and safe chemodynamic therapy (CDT)-based cancer treatment is expected but still faces challenges. Herein, a kind of multifunctional nanomicelles was constructed for CDT, combined with biocompatible polysaccharides as nanocarriers, pH responsiveness and active targeting of P-selectin overexpressed tumors. The P-selectin-targeted ligand, polyguluronate sulfate (PGS), complexed with copper peroxide to form PGS-Cu nanomicelles by electrostatic interactions. Under acidic conditions, PGS-Cu nanomicelles released copper ions with H₂O₂ and were able to produce •OH by Fenton-like reaction. In vitro data demonstrated PGS-Cu nanomicelles had high selectivity targeting P-selectin over-expressed cancer cells and induced cell death via CDT. In vivo evaluation showed PGS-Cu nanomicelles were enriched in tumor tissues and significantly inhibited tumor growth. This study identified that PGS-Cu nanomicelles could be a highly effective strategy for CDT cancer treatment.

Keywords: Anti-breast cancer; Chemodynamic therapy; P-selectin targeting; Polyelectrolyte nanomicelles; Polyguluronate sulfate.