Biomineralization-inspired Crystallization of Manganese Oxide on Silk Fibroin Nanoparticles for <i>in vivo</i> MR/fluorescence Imaging-assisted Tri-modal Therapy of Cancer

Abstract

Regenerated silk fibroin (SF) is a type of natural biomacromolecules with outstanding biocompatibility and biodegradability. However, stimulus-responsive SF-based nanocomplex has seldom been reported for application in tumor diagnosis and therapy. <b>Methods</b>: As a proof-of-concept study, a multifunctional SF@MnO₂ nanoparticle-based platform was strategically synthesized using SF as a reductant and a template <i>via</i> a biomineralization-inspired crystallization process in an extremely facile way. Because of their mesoporous structure and abundant amino and carboxyl terminal residues, SF@MnO₂ nanoparticles were co-loaded with a photodynamic agent indocyanine green (ICG) and a chemotherapeutic drug doxorubicin (DOX) to form a SF@MnO₂/ICG/DOX (SMID) nanocomplex. <b>Results</b>: The obtained product was highly reactive with endogenous hydrogen peroxide (H₂O₂) in tumor microenvironment, which was decomposed into O₂ to enhance tumor-specific photodynamic therapy (PDT). Moreover, SMID nanocomplex produced a strong and stable photothermal effect upon near-infrared (NIR) irradiation for photothermal therapy (PTT) owing to the distinct photothermal response of SF@MnO₂ and stably conjugated ICG<i>.</i> The concurrent NIR fluorescence and magnetic resonance (MR) imaging <i>in vivo</i> both indicated effective tumor-specific enrichment of SMID nanoparticles <i>via</i> enhanced permeability and retention (EPR) effect. Animal studies further verified that SMID nanoparticles remarkably improved tumor inhibitive efficacy through combination PTT/PDT/chemotherapy with minimal systemic toxicity or adverse effect. <b>Conclusion</b>: This study demonstrated the promising potential of SF-based nanomaterial to address some of the key challenges in cancer therapy due to unfavorable tumor microenvironment for drug delivery.