Light Delivery to Suppress Deep Tumor Growth

A team of scientists from the National University of Singapore (NUS) have succeeded in developing a method to wirelessly supply light into deep regions of the body to activate light-sensitive drugs for photodynamic therapy (PDT).

While PDT is considered to be a powerful light-induced cancer treatment, it is frequently restricted to surface cancers due to the low penetration of light via biological tissue. This wireless approach of light delivery allows PDT to be employed on the inner organs of the body with fine control. This technology could enable PDT to be employed for treating an extensive range of cancers, such as liver and brain cancer.

The study was headed by Professor Zhang Yong and Assistant Professor John Ho, who are respectively from the Department of Biomedical Engineering and Department of Electrical and Computer Engineering at NUS Faculty of Engineering. The findings of the study were featured in the scientific journal Proceedings of the National Academy of Sciences (PNAS) on 29 January 2018.

Our approach of light delivery will provide significant advantages for treating cancers with PDT in previously inaccessible regions. Powered wirelessly, the tiny implantable device delivers doses of light over long time scales in a programmable and repeatable manner. This could potentially enable the therapies to be tailored by the clinician during the course of treatment.

Assistant Professor John Ho

Asst Prof Ho also works as a Principal Investigator at the Biomedical Institute for Global Health Research and Technology (BIGHEART) at NUS.

Understanding Photodynamic Therapy

PDT is a treatment method that employs a light sensitive drug, known as a photosensitizer, which is activated by a particular wavelength of light, to generate a form of oxygen capable of killing neighboring cells. This offers a precision approach to cancer therapy that overcomes a number of the whole-body side effects of standard drugs such as chemotherapy. Besides directly killing cancer cells, PDT also destroys or shrinks tumors by damaging blood vessels in the tumor, thus avoiding the cancer cells from receiving essential nutrients. PDT could also trigger the immune system to attack the tumor cells.

However, PDT has thus far been restricted to the treatment of surface cancers. Standard light sources such as light-emitting diodes (LEDs) or lasers may be employed for surface tumors, such as skin cancer, but the low penetration of light via tissue restricts the depth to less than a centimeter. For the inner lining of some organs, such as the oesophagus, an endoscope – a thin, lighted tube used for looking at tissues present inside the body – can be employed for inserting a fiber optic cable, but it is not possible to access other regions in this manner. For organs such as the liver or brain, it is necessary for the organ to be exposed by surgery before using PDT.

Wireless Light Switch

The NUS team’s innovative approach of allowing PDT to be used for the inner organs of the body is accomplished by inserting a small wireless device at the target site, extending the temporal and spatial precision of PDT deep inside the body.

The miniaturized device, weighing 30 mg and is 15 mm³ in size, can be effortlessly implanted, and makes use of a wireless powering system for light delivery. After implanting the device at the target site, a specialized radio-frequency system wirelessly powers the device and then monitors the light-dosing rate.

The team succeeded in proving the therapeutic efficiency of this approach by triggering photosensitizers via thick tissues – more than three centimeters – unreachable by direct illumination, and by delivering multiple controlled doses of light in order to suppress tumor growth.

This novel approach enables ongoing treatment to prevent reoccurrence of a cancer, without additional surgery. The application of the technology can also be extended to many other light-based therapies, such as photothermal therapy, that face the common problem of limited penetration depth. We hope to bring these capabilities from bench to beside to provide new opportunities to shine light on human diseases.

Professor Zhang Yong

The team is presently working on producing nanosystems for targeted delivery of photosensitizers. They are also developing minimally invasive techniques in order to implant the wireless devices at the target site, and looking into incorporating sensors to the device in order to monitor the treatment response in real-time.

The Singapore Ministry of Education’s Tier 3 grant supported the study.