Concurrent chemoradiotherapy is used for advanced cancers, but the chemotherapy is dose limited by normal tissue toxicity. Localized X-ray activation of chemotherapy could overcome this, as studied here, with release from self-assembled nanomicelles (NMs) created from copolymers loaded with doxorubicin (DOX) having a photocleavable o-nitrobenzyl ester (o-Ne) group. The micelles demonstrated release of DOX from X-ray-induced Cherenkov light and conversion from a caged hydrophobic form to hydrophilic DOX, which achieves nuclear localization. Folate on the exterior of the NMs directed them for effective intracellular uptake prior to irradiation. Irradiation with 8 Gy released the DOX, which then entered the cell nucleus, providing near-complete in vivo tumor eradication and negligible off-target organ damage. Micelles were assembled from molecular component materials that are commonly in human use. This study realizes triple targeting in chemoradiation with potential for cell-receptor-mediated uptake, localized radiotherapy activation, and nuclear relocalization, all leading to limited off-target toxicity.

中文翻译：

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X 射线诱导切伦科夫光学触发笼式多柔比星释放到细胞核以进行放化疗激活。

同步放化疗用于晚期癌症，但化疗剂量受到正常组织毒性的限制。正如本文所研究的，化疗的局部 X 射线激活可以克服这一问题，通过从负载有阿霉素 (DOX) 的共聚物中释放自组装纳米胶束 (NM)，该纳米胶束具有可光裂解的邻硝基苯甲酯( o -Ne) 基团。胶束表现出 X 射线诱导的切伦科夫光释放 DOX，并从笼状疏水形式转化为亲水 DOX，从而实现核定位。NM 外部的叶酸引导它们在照射前进行有效的细胞内摄取。8 Gy 照射释放 DOX，然后进入细胞核，几乎完全根除体内肿瘤，并且脱靶器官损伤可以忽略不计。胶束由人类常用的分子成分材料组装而成。这项研究实现了放化疗中的三重靶向，具有细胞受体介导的摄取、局部放疗激活和核重新定位的潜力，所有这些都导致有限的脱靶毒性。