Bio-nanocomplexes with autonomous O₂ generation efficiently inhibit triple negative breast cancer through enhanced...

As one kind of aggressive cancer, triple-negative breast cancer (TNBC) has become one of the major causes of women mortality worldwide. Recently, combinational chemo-PDT therapy based on nanomaterials has been adopted for the treatment of malignant tumor. However, the efficacy of PDT was partly compromised under tumor hypoxia environment due to the lack of sustainable O₂ supply. In this study, CeO₂-loaded nanoparticles (CeNPs) with peroxidase activity were synthesized to autonomously generate O₂ by decomposing H₂O₂ within tumor region and reprogramming the hypoxia microenvironment as well. Meanwhile, the compound cinobufagin (CS-1) was loaded for inhibiting TNBC growth and metastasis. Moreover, the hybrid membrane camouflage was adopted to improve the biocompatibility and targeting ability of nanocomplexes. In vitro assay demonstrated that decomposition of H₂O₂ by CeO₂ achieved sustainable O₂ supply, which accordingly improved the efficacy of PDT. In turn, the generated O₂ improved the cytotoxicity and anti-tumor migration effect of CS-1 by downregulating HIF-1α and MMP-9 levels. In vivo assay demonstrated that the combination of CS-1 and PDT significantly inhibited the growth and distance metastasis of tumor in MDA-MB-231 bearing mice. Thus, this chemo-PDT strategy achieved satisfactory therapeutic effects by smartly utilizing the enzyme activity of nanodrugs and special micro-environment of tumor.