Platelet membrane-coated C-TiO_(2) hollow nanospheres for combined sonodynamic and alkyl-radical cancer therapy

The therapeutic efficiency of sonodynamic therapy(SDT)mainly depends on the presence of oxygen(O_(2))to generate harmful reactive oxygen species(ROS);thus,the hypoxic tumor microenvironment significantly limits the efficacy of SDT.Therefore,the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT.In this study,a biomimetic drug delivery system(C-TiO_(2)/AIPH@PM)composed of an alkyl-radical generator(2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride,AIPH)-loaded C-TiO_(2) hollow nanoshells(HNSs)as the inner cores,and a platelet membrane(PM)as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy.The PM encapsulation can significantly prolong the blood circulation time of CTiO_(2)/AIPH@PM compared with C-TiO_(2)/AIPH while enabling C-TiO_(2)/AIPH@PM to achieve tumor targeting.C-TiO_(2)/AIPH@PM can efficiently produce ROS and alkyl radicals,which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions.Furthermore,the generation of these radicals improves the efficiency of SDT.In addition,nitrogen(N_(2))produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold,thereby enhancing the penetration of CTiO_(2)/AIPH@PM at the tumor sites.Both in vitro and in vivo experiments demonstrate that CTiO_(2)/AIPH@PM possesses good biosafety,ultrasound imaging performance,and excellent anticancer efficacy.This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.

Biomimetic copper single-atom nanozyme system for self-enhanced nanocatalytic tumor therapy

Single-atom nanozymes(SAZs)with peroxidase(POD)-like activity have good nanocatalytic tumor therapy(NCT)capabilities.However,insufficient hydrogen peroxide(H2O2)and hydrogen ions in the cells limit their therapeutic effects.Herein,to overcome these limitations,a biomimetic single-atom nanozyme system was developed for self-enhanced NCT.We used a previously described approach to produce platelet membrane vesicles.Using a high-temperature carbonization approach,copper SAZs with excellent POD-like activity were successfully synthesized.Finally,through physical extrusion,a proton pump inhibitor(PPI;pantoprazole sodium)and the SAZs were combined with platelet membrane vesicles to create PPS.Both in vivo and in vitro,PPS displayed good tumor-targeting and accumulation abilities.PPIs were able to simultaneously regulate the hydrogen ion,glutathione(GSH),and H2O2 content in tumor cells,significantly improve the catalytic ability of SAZs,and achieve self-enhanced NCT.Our in vivo studies showed that PPS had a tumor suppression rate of>90%.PPS also limited the synthesis of GSH in cells at the source;thus,glutamine metabolism therapy and NCT were integrated into an innovative method,which provides a novel strategy for multimodal tumor therapy.