State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu 215123, China.
Institute of Functional Nano & Soft Materials (FUNSOM), & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, China.
Nanoscale. 2018 Aug 7;10(29):13976-13985. doi: 10.1039/c8nr03986k. Epub 2018 Jul 16.
Although chemo-radiotherapy has been widely applied in clinics for cancer treatment, current strategies still face many challenges including serious side-effects and drug resistance. Herein, we develop a chemically cross-linked poly-N,N'-dimethyl aminoethyl methacrylate (PDMAEMA) smart nanogel as an excellent thermosensitive nanocarrier to load both an anticancer drug, doxorubicin (DOX) and a radioisotope, I-labeled albumin, for enhanced chemo-radioisotope therapy. Such a PDMAEMA nanogel in the solution form at room temperature can be easily injected into a tumor, in which it would be transformed into a gel at body temperature. Sustained drug release occurs in the tumor owing to the pH sensitive switching activity of the nanogel. In addition, the in situ thermogelling behavior of PDMAEMA leads to the long-term retention of I-labeled albumin within the tumor. In vivo chemo-radiotherapy is then conducted, achieving excellent therapeutic efficacy due to the sustained drug release and I retention for a long time in the cancer lesions. Our newly developed strategy of using a thermosensitive polymer for enhancing chemo-radiotherapy may be considered as a promising platform for combined cancer therapy without inducing obvious side-effects compared to the traditional chemo or radiotherapy.
虽然化学放射疗法已广泛应用于癌症治疗的临床实践中，但目前的策略仍面临许多挑战，包括严重的副作用和耐药性。在此，我们开发了一种化学交联的聚 N,N'-二甲基氨基乙基甲基丙烯酸酯（PDMAEMA）智能纳米凝胶，作为一种出色的热敏纳米载体，用于负载抗癌药物阿霉素（DOX）和放射性同位素 I 标记白蛋白，以增强化疗同位素治疗。这种在室温下呈溶液形式的 PDMAEMA 纳米凝胶可轻松注射到肿瘤中，在体温下会转变为凝胶。由于纳米凝胶的 pH 敏感开关活性，药物会在肿瘤中持续释放。此外，PDMAEMA 的原位温敏胶凝行为导致 I 标记白蛋白在肿瘤内的长期保留。然后进行体内化疗同位素治疗，由于在癌症病灶中长时间持续释放药物和保留 I，从而实现了优异的治疗效果。与传统的化疗或放疗相比，我们使用热敏聚合物增强化疗同位素治疗的新策略可能被认为是一种有前途的联合癌症治疗平台，不会引起明显的副作用。
