The strategy of precise targeting and <i>in situ</i> oxygenating for enhanced triple-negative breast cancer chemophototherapy

Abstract

The absence of effective therapeutic targets and tumor hypoxia are the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Biomimetic nanotechnology and tumor microenvironment (TME) responsiveness bring hope and opportunity to address this problem. Here, we develop a core membrane nanoplatform (HM/D-I-BL) using hollow mesoporous manganese dioxide (HM) coated with a biomimetic cancer cell membrane for enhanced chemotherapy/phototherapy <i>via</i> the strategy of precise drug delivery and hypoxia amelioration. Cancer cell membrane modification endows HM/D-I-BL with excellent homologous targeting and immune escape performance. Cellular uptake and fluorescence imaging studies confirmed that HM/D-I-BL can be accurately delivered to tumor sites. HM/D-I-BL also features efficient <i>in situ</i> O₂ generation in tumors upon laser irradiation, and subsequently enhanced chemotherapy/phototherapy, pointing to its usefulness as a TME-responsive nanozyme to alleviate tumor hypoxia in the presence of H₂O₂. In addition, HM/D-I-BL showed good fluorescence and magnetic resonance imaging performances, which offers a reliable multimodal image-guided combination tumor therapy for precision theranostics in the future. In general, this intelligent biomimetic nanoplatform with its homotypic tumor targeting, <i>in situ</i> alleviation of tumor hypoxia and synergetic chemophototherapy would open up a new dimension for the precision treatment of TNBC.