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 (Bi 2 S 3 @mBi x Mn y O z nanosystem) was facilely constructed by directly using radiosensitizer Bi 2 S 3 nanorods (NRs) as a partial sacrificial template. Then, the chemotherapeutic drug doxorubicin (DOX) loaded PEGylated Bi 2 S 3 @mBi x Mn y O z nanosystem (PBmB-DOX) was constructed, which could realize tumor microenvironment (TME)-responsive drug release for chemotherapy sensitivity enhancement. And the Bi 2 S 3 NRs core could deposit more radiant energy to improve the radiotherapy sensitivity. Meanwhile, the compounds shell could catalyze H 2 O 2 to generate O 2 , 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 T 1 -MR imaging activation, which allowed on-demand tumor diagnosis. In this work, the synthetic strategy that directly using Bi 2 S 3 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.
Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics. Although the efficiencies of vaccines are limited, they can be enhanced by a well-designed antigen delivery system that promotes sufficient antigen presentation of dendritic cells (DCs) for initiating high T cell immunity. Herein, antigen-loaded manganese oxide (Mn 3 O 4 ) triangular-shaped ultrasmall nanoparticles were prepared to stimulate DC-based immunotherapy under the guidance of T 1 magnetic resonance imaging. The FDA-approved triblock copolymer Pluronic® F-68 was used not only to transfer the phase from hydrophobic to hydrophilic but also to enrich antigen loading and improve the biocompatibility of the prepared nanoparticles. Ovalbumin (OVA), a model antigen, was adsorbed on the surface of polymer-coated nanoparticles through electrostatic interaction to form Mn 3 O 4 @PF68-OVA nanoparticle-antigen complexes to stimulate DC-based immunization and antigen-specific T cell immunity. The Mn 3 O 4 @PF68-OVA nanovaccine (NV) induces negligible toxicity effects against 4T1 and bone marrow-derived dendritic cells (BMDCs) by conventional methods supports the proliferation of intestine organoids, which are an innovative three-dimensional cytotoxicity evaluation system, thereby indicating their potential safety for in vivo cancer therapies. The designed paramagnetic nanovaccine possessed excellent OVA delivery to dendritic-regulated antigen-specific T cells in vitro by stimulating the maturation level of BMDCs. In addition, Mn 3 O 4 @PF68-OVA NVs enhance immunity in vivo by increasing the T-cells and M1 macrophages, which suggests improved immunity. Excitingly, vaccination with Mn 3 O 4 @PF68-OVA offer complete protection in the prophylactic group and significant tumor inhibition in the therapeutic group against B16-OVA tumor. In addition, the designed nanovaccine demonstrated high T 1 -MR imaging in the tumor, further justifying enhanced tumor accumulation and capability to real-time monitor the treatment procedure. This study presents a promising nanosystem to design an effective nanovaccine for T 1 -MR imaging-guided tumor immunotherapy.
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