Rapid synthesis of 'yolk-shell'-like nanosystem for MR molecular and chemo-radio sensitization.

Abstract

Though amounts of attempts about nanomedicine for chemo-radiotherapy have been made, more efficient strategies for chemo-radio therapy enhancement still need to be studied and perfected. Herein, a 'yolk-shell'-like nanostructure (Bi2S3@mBixMnyOz nanosystem) was facilely constructed by directly using radiosensitizer Bi2S3 nanorods (NRs) as a partial sacrificial template. Then, the chemotherapeutic drug doxorubicin (DOX) loaded PEGylated Bi2S3@mBixMnyOz nanosystem (PBmB-DOX) was constructed, which could realize tumor microenvironment (TME)-responsive drug release for chemotherapy sensitivity enhancement. And the Bi2S3 NRs core could deposit more radiant energy to improve the radiotherapy sensitivity. Meanwhile, the compounds shell could catalyze H2O2 to generate O2, so as to alleviate tumor hypoxia for further chemo-radio therapy sensitization enhancement. More importantly, ferroptosis was participated in the process of PBmB-induced therapy via glutathione (GSH)-depletion mediated GPX4 inactivation, together with Mn ions induced chemodynamic therapy (Fenton-like reaction), which made additional contributions to increase the therapeutic efficacy. Last but not least, the GSH-stimulated degradation of compounds shell could contribute to self-enhanced T1-MR imaging activation, which allowed on-demand tumor diagnosis. In this work, the synthetic strategy that directly using Bi2S3 NRs as a partial sacrificial template to rapidly synthesize the 'yolk-shell'-like nanostructure for nanomedical application has rarely been reported before. And the in vitro and in vivo results suggest that our 'yolk-shell'-like PBmB-DOX nanosystem holds great promise to regulate TME for tumor-specific diagnosis and synergistic therapy.