Smart hydrothermally responsive microneedle for topical tumor treatment.

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) with 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.