Surface curvature-induced oriented assembly of sushi-like Janus therapeutic nanoplatform for combined chemodynamic therapy

Background Chemodynamic therapy (CDT) based on Fenton/Fenton-like reaction has emerged as a promising cancer treatment strategy. Yet, the strong anti-oxidation property of tumor microenvironment (TME) caused by endogenous glutathione (GSH) still severely impedes the effectiveness of CDT. Traditional CDT nanoplatforms based on core@shell structure possess inherent interference of different subunits, thus hindering the overall therapeutic efficiency. Consequently, it is urgent to construct a novel structure with isolated functional units and GSH depletion capability to achieve desirable combined CDT therapeutic efficiency. Results Herein, a surface curvature-induced oriented assembly strategy is proposed to synthesize a sushi-like novel Janus therapeutic nanoplatform which is composed of two functional units, a FeOOH nanospindle serving as CDT subunit and a mSiO(2) nanorod serving as drug-loading subunit. The FeOOH CDT subunit is half covered by mSiO(2) nanorod along its long axis, forming sushi-like structure. The FeOOH nanospindle is about 400 nm in length and 50 nm in diameter, and the mSiO(2) nanorod is about 550 nm in length and 100 nm in diameter. The length and diameter of mSiO(2) subunit can be tuned in a wide range while maintaining the sushi-like Janus structure, which is attributed to a Gibbs-free-energy-dominating surface curvature-induced oriented assembly process. In this Janus therapeutic nanoplatform, Fe3+ of FeOOH is firstly reduced to Fe2+ by endogenous GSH, the as-generated Fe2+ then effectively catalyzes overexpressed H2O2 in TME into highly lethal center dot OH to achieve efficient CDT. The doxorubicin (DOX) loaded in the mSiO(2) subunit can be released to achieve combined chemotherapy. Taking advantage of Fe3+-related GSH depletion, Fe2+-related enhanced center dot OH generation, and DOX-induced chemotherapy, the as-synthesized nanoplatform possesses excellent therapeutic efficiency, in vitro eliminating efficiency of tumor cells is as high as similar to 87%. In vivo experiments also show the efficient inhibition of tumor, verifying the synthesized sushi-like Janus nanoparticles as a promising therapeutic nanoplatform. Conclusions In general, our work provides a successful paradigm of constructing novel therapeutic nanoplatform to achieve efficient tumor inhibition.

Automated summary

In this study, a surface curvature-induced oriented assembly strategy was used to synthesize a sushi-like novel Janus therapeutic nanoplatform, which consists of two functional units, FeOOH nanospindles as the CDT subunit and mSiO(2) nanorods as the drug-loading subunit. The FeOOH CDT subunit is half covered by the mSiO(2) nanorod, forming a sushi-like structure. The FeOOH nanospindle is about 400 nm in length and 50 nm in diameter, while the mSiO(2) nanorod is about 550 nm in length and 100 nm in diameter. The FeOOH subunit can be reduced by endogenous GSH and catalyze H2O2 in TME to achieve efficient CDT, while the mSiO(2) subunit can release doxorubicin for combined chemotherapy.