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, Fe 3+ of FeOOH is firstly reduced to Fe 2+ by endogenous GSH, the as-generated Fe 2+ then effectively catalyzes overexpressed H 2 O 2 in TME into highly lethal ·OH to achieve efficient CDT. The doxorubicin (DOX) loaded in the mSiO 2 subunit can be released to achieve combined chemotherapy. Taking advantage of Fe 3+ -related GSH depletion, Fe 2+ -related enhanced ·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 ~ 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.