ScholarWorks@중앙대학교

초록

Implantable bioelectronics enable precise therapeutic interventions, particularly for brain disorders where local drug delivery is crucial. For glioblastoma (GBM) treatment, implantable drug delivery systems face significant challenges in achieving both mechanical compatibility and reliable wireless control. Dynamic changes in the tumor microenvironment present another major challenge, as temozolomide (TMZ) treatment triggers therapy-induced senescence (TIS), which paradoxically accelerates tumor progression, necessitating adaptive therapeutic capabilities. Developing systems that simultaneously address material constraints while enabling dynamic therapeutic responses remains a significant technical hurdle. Here, we developed a wireless-controlled implantable soft system utilizing phase-change materials with distinct melting points, enabling two-stage delivery of TMZ and senolytic drugs through eddy-current heating to clear senescent tumor cells in postoperative GBM management. In a mouse GBM model, our system achieved 60.4% greater tumor suppression than TMZ-only devices and demonstrated 63.6% improvement over oral gavage while reducing systemic toxicity. The system's versatility was shown in a breast cancer model with 73.9% higher tumor inhibition than intravenous doxorubicin. This work represents the first implementation of adaptive multistage release of chemotherapeutic and senolytic drugs in brain implantation-based delivery, effectively addressing TIS-associated problems with potential applications in other complex tumor scenarios.

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