Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117583, Singapore.
Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599, Singapore.
Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):1469-1474. doi: 10.1073/pnas.1717552115. Epub 2018 Jan 29.
An emerging class of targeted therapy relies on light as a spatially and temporally precise stimulus. Photodynamic therapy (PDT) is a clinical example in which optical illumination selectively activates light-sensitive drugs, termed photosensitizers, destroying malignant cells without the side effects associated with systemic treatments such as chemotherapy. Effective clinical application of PDT and other light-based therapies, however, is hindered by challenges in light delivery across biological tissue, which is optically opaque. To target deep regions, current clinical PDT uses optical fibers, but their incompatibility with chronic implantation allows only a single dose of light to be delivered per surgery. Here we report a wireless photonic approach to PDT using a miniaturized (30 mg, 15 mm) implantable device and wireless powering system for light delivery. We demonstrate the therapeutic efficacy of this approach by activating photosensitizers (chlorin e6) through thick (>3 cm) tissues inaccessible by direct illumination, and by delivering multiple controlled doses of light to suppress tumor growth in vivo in animal cancer models. This versatility in light delivery overcomes key clinical limitations in PDT, and may afford further opportunities for light-based therapies.
一类新兴的靶向治疗方法依赖于光作为空间和时间上精确的刺激源。光动力疗法 (PDT) 就是一个临床范例,其中光学照射选择性地激活光敏药物,即光增敏剂,在没有化疗等全身治疗相关副作用的情况下破坏恶性细胞。然而,PDT 和其他基于光的疗法的有效临床应用受到在生物组织中传递光的挑战的阻碍,生物组织对光不透明。为了靶向深部区域,目前的临床 PDT 使用光纤,但它们与慢性植入物的不兼容使得每次手术只能提供单次光剂量。在这里,我们报告了一种使用微型化(30 毫克,15 毫米)可植入装置和无线光传输系统的 PDT 无线光子方法。我们通过在无法直接照射的厚 (>3 厘米) 组织中激活光敏剂(氯乙酮 6),并通过输送多次受控剂量的光来抑制动物癌症模型中的肿瘤生长,证明了这种方法的治疗效果。这种在光传输方面的多功能性克服了 PDT 的关键临床限制,并可能为基于光的治疗方法提供更多机会。