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.

Noncoding RNAs:the shot callers in tumor immune escape

Immunotherapy,designed to exploit the functions of the host immune system against tumors,has shown considerable potential against several malignancies.However,the utility of immunotherapy is heavily limited due to the low response rate and various side effects in the clinical setting.Immune escape of tumor cells may be a critical reason for such low response rates.Noncoding RNAs(ncRNAs)have been identified as key regulatory factors in tumors and the immune system.Consequently,ncRNAs show promise as targets to improve the efficacy of immunotherapy in tumors.However,the relationship between ncRNAs and tumor immune escape(TIE)has not yet been comprehensively summarized.In this review,we provide a detailed account of the current knowledge on ncRNAs associated with TIE and their potential roles in tumor growth and survival mechanisms.This review bridges the gap between ncRNAs and TIE and broadens our understanding of their relationship,providing new insights and strategies to improve immunotherapy response rates by specifically targeting the ncRNAs involved in TIE.