Infrared excitable nanoparticle-based photosensitizers for targeted photodynamic therapy

近年来，光动力疗法作为一种治疗癌症的技术已经被人们所接受。它利用光敏剂在适当波长的光照射下局部治疗目标组织。人们普遍认为，光动力疗法的机制是基于被激发的光敏剂与周围分子的相互作用，产生活性氧，然后对生物底物造成损伤，最终导致细胞死亡。然而，光动力疗法存在着主要的缺陷和局限性，需要提高其疗效以充分发挥其潜力。本项目的目的是设计和开发基于光子上转换纳米粒子的靶向光动力治疗的红外可激发光敏剂。假设提案中讨论的光敏剂设计将(1)具有更深的组织穿透；(2)对目标具有高度特异性；(3)就所包括的光活化分子和所附着的靶向剂的类型而言是通用的。本提案将着重于这些纳米粒子光敏剂的设计、工程和体外生物测试。这个项目将是第一个遵循这种策略的研究。纳米光敏剂的开发将解决光动力治疗中组织穿透深度的问题，使其更有可能应用于光动力治疗深部组织癌症。随着光动力治疗药物开发的不断推进，将光动力治疗用于癌症治疗，特别是与辅助治疗相结合，将成为可能。所解决的问题可以为下一代光动力治疗药物的开发奠定基础，并改善癌症治疗的光动力疗法。研究结果将通过在同行评议的期刊和会议上发表文章来传播。通过在项目中包括研究生、本科生和当地高中生，教育将是拟议研究的一个组成部分。代表性不足的群体的学生将被招募参加研究项目。

0931677ZhangPhotodynamic therapy has gained acceptance as a technique for cancer treatment in recent years. It utilizes a photosensitizer to treat the target tissue locally upon the irradiation with light of appropriate wavelengths. It is generally accepted that the mechanism of photodynamic therapy is based on the interaction between the excited photosensitizer and surrounding molecules, generating reactive oxygen species, which will then cause damage to biological substrates and ultimately cell death. Yet, photodynamic therapy suffers from major drawbacks and limitations, and needs improvement in its efficacy to reach the full potential. The objective of this project is to design and develop infrared excitable photosensitizers for targeted photodynamic therapy, based on photon upconverting nanoparticles. It is hypothesized that photosensitizers of the design discussed in the proposal will (1) have deeper tissue penetration; (2) be highly specific to the target; and (3) be versatile, with regard to the types of photoactivated molecules included and of targeting agents attached. This proposal will focus on the design, engineering and in vitro biological tests of these nanoparticle-based photosensitizers. This project will be the first study following such strategy. The development of the proposed nanoparticle-based photosensitizers would address the tissue penetration depth issue in photodynamic therapy, and make it more feasible to apply for treatments of deep-tissue cancers.With the advancement of photodynamic therapy drug development, it will become feasible to use photodynamic therapy for cancer treatments, especially when in combination with adjuvant therapies. The issues addressed could set the stage for the development of next generation photodynamic therapy drugs, and the improvement of photodynamic therapy for cancer treatment. Results of the research will be disseminated through contributions in peer-reviewed journals, and conference contributions. Education will be an integral part of the proposed research by including graduate, undergraduate students and local high school student(s) in the projects. Students of underrepresented groups will be recruited to participate in the research program.