Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, China; Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan 430030, China.
J Control Release. 2023 Jun;358:566-578. doi: 10.1016/j.jconrel.2023.05.008. Epub 2023 May 17.
Locoregional therapy has attracted increasing attention for subcutaneous tumors owing to its merits of minimally invasive operation and negligible systematic toxicity. However, to accelerate clinical translation, further promotions in deep-seated penetration, temporal-spatial controllability, personalized adaptability, as well as easy operation are still urgently needed. This work proposed a self-heating-cooking-package-inspired hydrothermally responsive multi-round acturable microneedle (HRMAM) system, which loaded docetaxel (DTX) in the polycaprolactone (PCL), to serve as deeply penetrable, hydrothermal-chemotherapy synergetic, on-demand and self-service anti-tumor treatment. The optimized hydrothermally responsive formulation served as base components for water-based self-heating responsive drug release with synergistic anti-tumor thermal therapy, and simultaneously in combination with well-designed grooved-structure needle tips for directional deep delivery and enhanced transfer efficiency. To satisfy spatial precision and flexible controllability, this engineering-based detachable HRMAM system was divided into three relatively independent segments, which were fitted perfectly with an original-designed applicator for ensuring easy operation in a smart self-service manner. Impressively, the HRMAM system achieved encouraging tumor growth inhibition of 75.11% and 72.29% in animal model of melanomas and breast carcinoma, respectively, much higher than those of other groups receiving traditional treatment, without obvious side effects. It was anticipated that the HRMAM system would manifest great promise to combat unreachable and deep-seated subcutaneous tumors, bellowing clinical values upon locoregional therapy products with high efficiency, low toxicity, flexible controllability, temporal-spatial precision, easy operation, as well as patient's painless, comfort and compliance.
局部区域治疗因其微创操作和系统毒性极小的优点，引起了人们对皮下肿瘤的越来越多的关注。然而，为了加速临床转化，仍然迫切需要进一步提高深层渗透、时空可控性、个性化适应性以及操作简便性。本工作提出了一种自加热烹饪包启发的水响应多轮可控性微针（HRMAM）系统，该系统将多西紫杉醇（DTX）装载到聚己内酯（PCL）中，作为可深层渗透、水热化疗协同、按需和自助式抗肿瘤治疗。优化的水响应配方作为水基自加热响应药物释放的基础成分，具有协同抗肿瘤热疗作用，同时与设计良好的槽形结构针尖结合，实现定向深层传递和增强传递效率。为了满足空间精度和灵活可控性，基于工程的可拆卸 HRMAM 系统分为三个相对独立的部分，与原始设计的敷贴器完美适配，确保以智能自助方式轻松操作。令人印象深刻的是，HRMAM 系统在黑色素瘤和乳腺癌动物模型中分别实现了 75.11%和 72.29%的肿瘤生长抑制作用，明显高于接受传统治疗的其他组，没有明显的副作用。预计 HRMAM 系统将在局部区域治疗产品中具有高效、低毒性、灵活可控性、时空精度、操作简便以及患者无痛、舒适和依从性等方面，具有很大的应用前景，能够对抗难以触及和深层的皮下肿瘤。
