School of Pharmacy, Jiangsu Key Laboratory of Inflammation and Molecular Drug Targets, Nantong University, Nantong, Jiangsu 226001, China.
Department of Pharmacy, Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215009, China.
ACS Appl Mater Interfaces. 2021 Oct 27;13(42):49671-49681. doi: 10.1021/acsami.1c13249. Epub 2021 Oct 15.
As a kind of high linear energy transfer (LET) radiation, internal conversion electrons are emitted from some radionuclides, such as I, triggering severe DNA damage to tumor cells when transported into the nucleus. Herein, we develop a curcumin-loaded nanomicelle composed of a photosensitizer chlorin e6 (Ce6) and amphiphilic poly(ethylene glycol) (poly(maleic anhydride--1-octadecene)-poly(ethylene glycol) (C-PMH-PEG)) to deliver I into the nucleus under 660 nm laser irradiation, leading to the optimized imaging-guided internal conversion electron therapy of cancer. Ce6-containing nanomicelles (Ce6-C-PEG) self-assemble with nucleus-targeted curcumin (Cur), obtaining Ce6-C-PEG/Cur nanoparticles. After labeling Cur with I, Ce6-C-PEG/Cur enables single-photon emission computed tomography and fluorescence imaging of the tumor, serving as a guide for follow-up laser irradiation. Notably, the 660 nm laser-triggered photodynamic reaction of Ce6 optimizes the delivery of Ce6-C-PEG/I-Cur at various stages, including tumor accumulation, cellular uptake, and lysosome escape, causing plenty of I-Cur to enter the nucleus. By this strategy, Ce6-C-PEG/I-Cur showed optimal antitumor efficacy and high biosafety in mice treated with local 660 nm laser irradiation using efficient energy deposition of internally converted electrons over short distances. Therefore, our work provides a novel strategy to optimize I delivery for tumor treatment.
作为一种高线性能量转移 (LET) 辐射，内转换电子由一些放射性核素如 I 发射，当它们进入细胞核时，会引发肿瘤细胞严重的 DNA 损伤。在此，我们开发了一种载有姜黄素的纳米胶束，由光敏剂氯乙酮 (Ce6) 和两亲性聚乙二醇 (聚(马来酸酐-1-十八烯)-聚乙二醇) (C-PMH-PEG) 组成，在 660nm 激光照射下将 I 递送至细胞核，从而实现了癌症的优化成像引导内转换电子治疗。含有 Ce6 的纳米胶束 (Ce6-C-PEG) 与核靶向姜黄素 (Cur) 自组装，得到 Ce6-C-PEG/Cur 纳米颗粒。用 I 标记 Cur 后，Ce6-C-PEG/Cur 可以进行单光子发射计算机断层扫描和肿瘤荧光成像，作为后续激光照射的指导。值得注意的是，660nm 激光触发的 Ce6 光动力反应优化了 Ce6-C-PEG/I-Cur 在肿瘤积累、细胞摄取和溶酶体逃逸等各个阶段的递药，导致大量的 I-Cur 进入细胞核。通过这种策略，Ce6-C-PEG/I-Cur 在接受局部 660nm 激光照射的小鼠中表现出最佳的抗肿瘤疗效和高生物安全性，这是由于内转换电子在短距离内的高效能量沉积。因此，我们的工作为优化 I 用于肿瘤治疗的递送提供了一种新策略。
