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

Abstract

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.

An Ultrasonically Powered Implantable Microprobe for Electrolytic Ablation

“…Additionally, the regional peak intensities tend to concentrate along the center axis of the transducer (with a measured intensity of 120 mW/cm 2 at a distance of 25 cm from the transducer). Such a long working distance is sufficient for most deeply seated solid tumors 20,26 .…”

“…Ultrasonic power allows the device to be miniaturized to dimensions (mm-scale) that are not feasible using traditional inductive wireless powering methods 15 . In addition, ultrasound has a long operation range (>10 cm) 15-20 and a higher power transfer efficiency than traditional inductive power at mm-scale reviver sizes 15 , and it is significantly less sensitive to angular misalignment between the transmitter and the receiver 15,17,[20][21][22][23] . The implantable microprobe may increase the clinical relevance of EA by allowing wireless control over device operation (capability to remotely turn the device on and off) and providing flexibility in treatment options (easier to administer fractionated doses over a longer period).…”

The photon in the revolution of medicine of the 21st century

“…En PDT es crucial el control de los parámetros clave la luz con la que se activan los PS específicos: i) tipo de fuente (LED, Láser, emisión continua o pulsada); ii) su longitud de onda; iii) su fluencia; iv) energía luminosa depositada localmente en cada parte del tumor, etc. Las fuentes se luz para PDT es un campo vital en continuo desarrollo en el que queda mucho trabajo investigador por efectuar [36].…”

Endoscopic Probe for Ultrasound-Assisted Photodynamic Therapy of Deep-Lying Tissue

“…Note that the absorbance of endogenous chromophores is low within the NIR window, so that the energy loss of irradiated light due to light absorption can be minimized. Implantable light sources can be used to reduce the distance that the light travels to the tumor site [19] if a module capable of elaborate insertions is available to avoid tissue perforation. As another approach, we proposed a way to mitigate the adverse effect of optical scattering itself on the penetration depth of light [20].…”