DNA Nanoclusters Combined with One-Shot Radiotherapy Augment Cancer Immunotherapy Efficiency

Yuexia Xie; Huishan Li; Lei XuHanbing ZouXingang WangXiaozhen HeQianyun TangYan ZhouXue ZhaoXiaojing ChenHongmei LiuJun PuDan LuoPeifeng Liu

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DNA Nanoclusters Combined with One-Shot Radiotherapy Augment Cancer Immunotherapy Efficiency

机译：DNA Nanoclusters Combined with One-Shot Radiotherapy Augment Cancer Immunotherapy Efficiency

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Immunotherapy shows immense promise for improving cancer treatment.Combining immunotherapy with radiotherapy provides a conspicuousadvantage due to its enhanced abscopal effect. However, established immunetolerance mechanisms in the tumor microenvironment can hamper thegeneration of a sufficient abscopal effect. Herein, a type of DNA nanocluster(DNAnc) that is self-assembled by a CpG-ODNs-loaded Y-shaped doublestrandedDNA vector based on the unique complementary base-pairing rulesis designed. The unique structure of DNAnc makes it load more than≈8125.5 ± 822.5 copies of CpG ODNs within one single nanostructure, whicheffectively increases resistance to nuclease degradation and elevates theefficiency of repolarizing macrophages to an M1-like phenotype. Mechanisticstudies reveal that more DNAncs are endocytosed by macrophages in thecancer tissue and repolarized macrophages to elicit a robust abscopal effectwith the accumulation of macrophages induced by radiotherapy, generatingpotent, long-term, and durable antitumor immunity for the inhibition oftumor metastasis and the prevention of tumor recurrence, which provides anovel strategy to boost cancer immunotherapy.

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来源
《Advanced Materials》 |2023年第17期|2208546.1-2208546.14|共14页
作者
Yuexia Xie; Huishan Li; Lei XuHanbing ZouXingang WangXiaozhen HeQianyun TangYan ZhouXue ZhaoXiaojing ChenHongmei LiuJun PuDan LuoPeifeng Liu;
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State Key Laboratory of Oncogenes and Related GenesShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200032, China,Central LaboratoryRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 20012;

State Key Laboratory of Oncogenes and Related GenesShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200032, China;

Department of Radiation OncologyRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127, ChinaMicro-Nano Research and Diagnosis CenterRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127, ChinaMicro-Nano Research and Diagnosis CenterRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127, China,Department of Biological and Environmental EngineeringCornell UniversityIthaca, NY 14853, USAState Key Laboratory of Oncogenes and Related GenesShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200032, China,Micro-Nano Research and Diagnosis CenterRen Ji HospitalSchool of MedicineShanghai Jiao Tong Un;

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DNA nanoclusters; immunotherapy; macrophages; radiotherapy; tumor microenvironment reprogramming;

DNA Nanoclusters Combined with One-Shot Radiotherapy Augment Cancer Immunotherapy Efficiency

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