Zhang Zhifan, Li Lin, Ge Yuchen, Chen Anni, Diao Shanchao, Yang Yueling, Chen Qianyue, Zhou Yingling, Shao Jie, Meng Fanyan, Yu Lixia, Tian Manman, Qian Xiaoping, Lin Zhaoyu, Xie Chen, Liu Baorui, Li Rutian
The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
Clinical Cancer Institute, Nanjing University, Nanjing, 210008, China.
Adv Sci (Weinh). 2025 May;12(20):e2413387. doi: 10.1002/advs.202413387. Epub 2025 Apr 15.
In situ radiotherapy is the most successful cytotoxic therapy available for the treatment of solid tumors, while high-dose radiotherapy per fraction is not yet widely and reliably used. To some extent, the major considerations of the disappointing results are on the risk of high-dose irradiation-induced damage to the surrounding normal tissues and the difficulty in distant metastasis control. To break these restraints, a gelatinase-responsive amphiphilic methoxypolyethyleneglycol-PVGLIG-polycaprolactone (mPEG-PVGLIG-PCL) nanoparticles' loading verteporfin (N@VP), a special photosensitizer that can also be excited by X-rays to produce cytotoxic singlet oxygen and greatly enhance radiotherapy efficacy, is prepared in this study. Herein, it is shown that the formed N@VP combined with conventional-dose radiation therapy (RT, 2 Gy (gray, a radiation dose unit)) can realize an antitumor effect no less than high-dose RT (8 Gy) and minimize radiation dose necessary to achieve local tumor control. Moreover, this radiosensitive nanosystem can exert excellent systemic antitumor immunity and abscopal effect, providing a preferable "in situ vaccine" strategy based on conventional-dose RT to achieve efficient systemic management of distant tumor metastasis. When combined with immunotherapy, this novel strategy for radiosensitization results in better immunotherapy sensitivity by stimulating significant immunogenic tumor cell death and synergistic antitumor immune responses.
原位放射疗法是治疗实体瘤最成功的细胞毒性疗法,而高剂量分次放射疗法尚未得到广泛且可靠的应用。在某种程度上,结果令人失望的主要原因在于高剂量照射对周围正常组织造成损伤的风险以及远处转移控制的难度。为突破这些限制,本研究制备了一种明胶酶响应性两亲性甲氧基聚乙二醇 - PVGLIG - 聚己内酯(mPEG - PVGLIG - PCL)纳米粒负载维替泊芬(N@VP),维替泊芬是一种特殊的光敏剂,也可被X射线激发产生细胞毒性单线态氧并极大增强放射治疗效果。在此表明,形成的N@VP与传统剂量放射疗法(RT,2戈瑞(戈瑞,辐射剂量单位))联合使用可实现不低于高剂量RT(8戈瑞)的抗肿瘤效果,并将实现局部肿瘤控制所需的辐射剂量降至最低。此外,这种放射敏感纳米系统可发挥出色的全身抗肿瘤免疫和远隔效应,为基于传统剂量RT实现对远处肿瘤转移的有效全身管理提供了一种较好的“原位疫苗”策略。当与免疫疗法联合使用时,这种新型放射增敏策略通过刺激显著的免疫原性肿瘤细胞死亡和协同抗肿瘤免疫反应,使免疫疗法敏感性更高。
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