1. Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, School of Materials and Energy, Southwest University, Chongqing 400715, China.
2. Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing 400715, China.
3. Institute of Sericulture and Systems Biology, Southwest University, Chongqing 400716, China.
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.
Methods: As a proof-of-concept study, a multifunctional SF@MnO2 nanoparticle-based platform was strategically synthesized using SF as a reductant and a template via 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.
Results: 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. The concurrent NIR fluorescence and magnetic resonance (MR) imaging in vivo both indicated effective tumor-specific enrichment of SMID nanoparticles via 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.
Conclusion: 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.
Keywords: Silk fibroin, Tumor microenvironment, Combination therapy, MR/fluorescence imaging, Manganese Oxide.