Low-cost photodynamic therapy devices for global health settings: Characterization of battery-powered LED performance and smartphone imaging in 3D tumor models.

Joshua Hempstead,Dustin P Jones,Jonathan P Celli,Imran Rizvi,Tayyaba Hasan,Abdelali Ziouche,Gwendolyn M Cramer,Stephen Arnason

doi:10.1038/srep10093

Abstract

A lack of access to effective cancer therapeutics in resource-limited settings is implicated in global cancer health disparities between developed and developing countries. Photodynamic therapy (PDT) is a light-based treatment modality that has exhibited safety and efficacy in the clinic using wavelengths and irradiances achievable with light-emitting diodes (LEDs) operated on battery power. Here we assess low-cost enabling technology to extend the clinical benefit of PDT to regions with little or no access to electricity or medical infrastructure. We demonstrate the efficacy of a device based on a 635 nm high-output LED powered by three AA disposable alkaline batteries, to achieve strong cytotoxic response in monolayer and 3D cultures of A431 squamous carcinoma cells following photosensitization by administering aminolevulinic acid (ALA) to induce the accumulation of protoporphyrin IX (PpIX). Here we characterize challenges of battery-operated device performance, including battery drain and voltage stability specifically over relevant PDT dose parameters. Further motivated by the well-established capacity of PDT photosensitizers to serve as tumour-selective fluorescence contrast agents, we demonstrate the capability of a consumer smartphone with low-cost add-ons to measure concentration-dependent PpIX fluorescence. This study lays the groundwork for the on-going development of image-guided ALA-PDT treatment technologies for global health applications.

Highlights

A lack of access to effective cancer therapeutics in resource-limited settings is implicated in global cancer health disparities between developed and developing countries
We evaluate the capabilities of battery powered portable light-emitting diodes (LEDs)-based light sources for aminolevulinic acid (ALA)-based photodynamic therapy (PDT) and tumour imaging
For treatment we show that a source powered by disposable alkaline batteries has sufficient stability for accurate dosimetry and achieves nearly complete cytotoxic response in 3D cultures of squamous carcinoma cells

Summary

Introduction

A lack of access to effective cancer therapeutics in resource-limited settings is implicated in global cancer health disparities between developed and developing countries. A complex set of contributing factors are implicated including variable prevalence of risk factors such as smoking, chewing tobacco, infectious agents; limited access to sophisticated medical screening and imaging for timely cancer detection; and limited availability of cancer therapeutics in resource limited settings In this context, we consider the potential role of photodynamic therapy (PDT), a light-based treatment modality in which wavelength-specific activation of a photosensitizing molecule that accumulates selectively in malignant tissue is used to provide site-directed tumour destruction[3]. In the context of cancer treatment technologies suitable for resource limited settings, it is crucial to consider that electrical power is often unavailable or may not be sufficiently reliable and stable for clinical procedures With this in mind it is significant to note that the development of high output light-emitting diodes (LEDs) capable of providing exactly the required illumination in a handheld format, powered by only a few volts from standard consumer batteries, suggests the potential for PDT with a low-cost, portable, battery-powered device. Clinical studies of PDT for oral cancer treatment collectively indicate that PDT is a safe and effective approach, with remarkable healing of the mucosa, and it is effective for early stage cancerous and precancerous lesions of the oral cavity[4,7,16,17,18,19,20]

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Results

Conclusion