The strategy of precise targeting and in situ 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 via 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 in situ 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, in situ alleviation of tumor hypoxia and synergetic chemophototherapy would open up a new dimension for the precision treatment of TNBC.