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

Nano Research 2023年第1期16卷 782-791页

作者： Weihong Guo Tao Wang Chunyu Huang Shipeng Ning Qinglong Guo Wei Zhang Huawei Yang Daoming Zhu Qinqin Huang Haisheng Qian Xianwen Wang Department of Molecular Pathology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450014China Department of Orthopaedics The Second Hospital of Anhui Medical UniversityHefei 230601China School of Biomedical Engineering Research and Engineering Center of Biomedical MaterialsAnhui Medical UniversityHefei 230032China Department of General Surgery&Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor Nanfang HospitalThe First School of Clinical MedicineSouthern Medical UniversityGuangzhou 510515China Department of Radiation and Medical Oncology Hubei Key Laboratory of Tumor Biological BehaviorsHubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Breast Surgery Guangxi Medical University Cancer HospitalNanning 530000China

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.

关键词： C-TiO_(2) sonodynamic therapy alkyl-radical therapy combination therapy biomimetic nanomaterials

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