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

Abstract

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.

Keywords

• manganese oxide
• nanoparticles
• silk fibroin tumor microenvironments
• tumor therapy