Theranostics 2019; 9(21):6314-6333. doi:10.7150/thno.36252
Biomineralization-inspired Crystallization of Manganese Oxide on Silk Fibroin Nanoparticles for in vivo MR/fluorescence Imaging-assisted Tri-modal Therapy of Cancer
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.
Yang R, Hou M, Gao Y, Lu S, Zhang L, Xu Z, Li CM, Kang Y, Xue P. Biomineralization-inspired Crystallization of Manganese Oxide on Silk Fibroin Nanoparticles for in vivo MR/fluorescence Imaging-assisted Tri-modal Therapy of Cancer. Theranostics 2019; 9(21):6314-6333. doi:10.7150/thno.36252. Available from http://www.thno.org/v09p6314.htm
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.