Biomimetic Nucleation of Manganese Oxide on Silk Fibroin Nanoparticles for Designing Raspberry-Structured Tumor Environment-Responsive Anticancer Nanocarriers

Bombyx mori silk fibroin is a natural biomacromolecule that can be assembled into nanoparticles. Manganese dioxide (MnO₂) is responsive to tumor microenvironment (TME). Herein, SF and MnO₂ is integrated to develop novel TME-responsive drug carriers. Specifically, silk fibroin nanoparticles (SF-NPs) are used as a biotemplates to regulate the nucleation and self-assembly of MnO₂ for designing the complex drug delivery (SM-NPs). The SM-NPs are further modified by polyethylene glycol and folic acid to improve their stability and tumor targeting. The resultant nanocarriers (SMPF-NPs) present a raspberry-like structure with lamellar MnO₂ nanoparticles coating on its surface. The SMPF-NPs show a high drug-loading capability and selectively release drugs in acidic TME. Due to the catalytic activity of MnO₂, the SMPF-NPs generate high levels of oxygen under H₂O₂ and produce more reactive oxygen after loading Ce6. In vivo and in vitro analysis prove that SMPF-NPs can accumulate in breast tumor tissues, efficiently kill cancer cells, and destroy breast cancer tumors by a combination of chemotherapy and photodynamic therapy (PDT). Moreover, the SMPF-NPs also provide fluorescence and magnetic resonance (MR) imaging for guiding cancer therapy. These results suggest that the self-assembled SF and MnO₂ nanocomplex could be a novel TME-responsive nanodrug delivery system.