Ultrasound Wirelessly Controlled Electrically Responsive Implantable Drug Delivery System for Enhanced Tumor Therapy.

Implantable controlled local drug delivery offers many advantages over systemic delivery. However, wirelessly controlling drug release from implanted devices via exogenous stimulation remains challenging. Herein, an ultrasound wirelessly controlled electrically responsive implantable drug delivery system (UI-TENG-IDDS) is proposed, which consists of an ultrasound-driven implantable triboelectric nanogenerator (UI-TENG) and an electrically responsive drug reservoir. When ultrasound is applied to the skin, it induces high-frequency vibrations in the UI-TENG, generating pulsed electrical output (≈50 µA at 9 V) to electrolyze water, thereby increasing the alkalinity near the cathode and dissolving drug carrier (co-PMMA) to release drugs. Moreover, UI-TENG-IDDS can accelerate the diffusion of negatively charged drugs via iontophoresis mechanism. Methotrexate (MTX) loaded UI-TENG-IDDS has been applied to ablate tumors without causing evident side effects. The UI-TENG-IDDS can wirelessly control drug release without complex electronic design and the electrical outputs are not limited by the battery life and capacity, avoiding battery replacement surgery. Considering the advantage that TENG can be fabricated using biodegradable and biocompatible materials, this work provides an efficient, economical, and safe regimen for spatiotemporal controlled implantable drug delivery.