An Implantable Ultrasonically-Powered Micro-Light-Source (µLight) for Photodynamic Therapy

摘要

Photodynamic therapy (PDT) is a promising cancer treatment modality that can selectively target unresectable tumors through optical activation of cytotoxic agents, thus reducing many side effects associated with systemic administration of chemotherapeutic drugs. However, limited light penetration into most biological tissues have so far prevented its widespread adoption beyond dermatology and a few other oncological applications in which a fiber optic can be threaded to the desired locations via an endoscopic approach (e.g., bladder). In this paper, we introduce an ultrasonically powered implantable microlight source, μLight, which enables in-situ localized light delivery to deep-seated solid tumors. Ultrasonic powering allows for small receiver form factor (mm-scale) and power transfer deep into the tissue (several centimeters). The implants consist of piezoelectric transducers measuring 2 × 2 × 2 mm³ and 2 × 4 × 2 mm³ with surface-mounted miniature red and blue LEDs. When energized with 185 mW/cm² of transmitted acoustic power at 720 kHz, μLight can generate 0.048 to 6.5 mW/cm² of optical power (depending on size of the piezoelectric element and light wavelength spectrum). This allows powering multiple receivers to a distance of 10 cm at therapeutic light output levels (a delivery of 20–40 J/cm² light radiation dose in 1–2 hours). In vitro tests show that HeLa cells irradiated with μLights undergo a 70% decrease in average cell viability as compared to the control group. In vivo tests in mice implanted with 4T1-induced tumors (breast cancer) show light delivery capability at therapeutic dose levels. Overall, results indicate implanting multiple µLights and operating them for 1–2 hours can achieve cytotoxicity levels comparable to the clinically reported cases using external light sources.