Implantable Therapeutic Devices: Bridging the Gap Between Systemic and Localized Cancer Therapy

Systemic chemotherapy remains central to cancer treatment but is limited by nonspecific biodistribution, dose- limiting toxicity, and poor penetration into solid tumors. Nanomedicine has improved pharmacokinetics and targeting, yet most nanoparticles fail to accumulate meaningfully within tumors due to biological clearance and stromal barriers. Implantable drug-delivery systems (IDDS), particularly micro-reservoir platforms enabled by microelectromechanical systems (MEMS), have emerged as a promising strategy to overcome these limitations by placing therapeutics directly at or within the tumor site. This review synthesizes the evolution of implantable devices from early passive polymers and osmotic pumps to modern programmable microchips with electronically triggered reservoirs, wireless control, and integrated sensors. The engineering foundations of reservoir architecture, membrane activation, and energy management are discussed in relation to pharmacological benefits, including high intratumoral concentrations, reduced systemic toxicity, improved drug stability, and precise spatiotemporal control of mono- and multi-agent regimens. Preclinical evidence across breast, pancreatic, glioblastoma, melanoma, prostate, head-and-neck cancers, and sarcomas demonstrates enhanced tumor penetration and therapeutic efficacy with substantially lower systemic exposure. Emerging smart implants incorporating real-time monitoring and AI-assisted dosing represent the next step toward adaptive, patient-specific therapy. Despite strong promise, translation to the clinic requires addressing challenges in biocompatibility, foreign-body response, drug stability, manufacturing scalability, regulatory pathways, and patient acceptance. Overall, micro-reservoir implantable systems offer a transformative path toward precision local oncology by shifting therapeutic control from systemic circulation to the tumor microenvironment itself, enabling more effective and individualized cancer treatment.