Two birds with one stone: triple negative breast cancer therapy by PtCo bimetallic nanozyme coated with gemcitabine-hyaluronic acid-polyethylene glycol

Abstract

For the treatment of triple-negative breast cancer (TNBC), without expression of estrogen, progesterone and HER2 receptors, specific treatment guideline is still under criticism, especially in tumor hypoxia. But assuming the molecular similarity of TNBC with breast cancer gene-1-related cancers, gemcitabine may be used in TNBC treatment on the nanozyme platform combined with photodynamic therapy (PDT). After designing the nanozyme with four components, platinum–cobalt: with catalase/peroxidase capabilities, hyaluronic acid: nanozyme targeting by interacting with CD44 receptor, poly[ethylene glycol]: water-soluble macromolecule for immune escape, and Gem: antitumor drug, its physicochemical properties was investigated by thermogravimetric, X-ray diffraction and energy dispersive X-ray, and therapeutic effects in in vitro and in vivo. The results show that platinum–cobalt@gemcitabine-hyaluronic acid-polyethylene glycol (PtCo@Gem-HA-PEG) especially synergized with PDT has high toxicity on 4T1 cells and tumor by enhancing the catalase-/peroxidase-like activities to produce O2, O2•− and •OH, and increase the intracellular free radicals. PtCo@Gem-HA-PEG inhibits tumor development by increasing drug accumulation in the tumor and enhancing apoptotic mechanisms through synergistic activity with PDT. Nevertheless, the major organ damage confirmed by the histological method in the long-term application of PtCo@Gem-HA-PEG, makes their application challenging due to permanent catalytic activity. However, results of improved drug permeability based on reduced hypoxia, higher drug retention, and enzyme-like activity that could be synergized with other therapeutic approaches like a PDT, have made their use attractive. Hence, this study provides a promising path in the TNBC treatment by nanozymes, which requires further toxicological investigations.Graphic