Novel Nanostructures for Topical Photodynamic Therapy

描述(由申请人提供)： 本建议的目的是合成和评价新型碳基纳米结构光敏剂(PS)，用于通过局部光动力疗法(PDT)局部治疗各种非黑色素瘤、癌前和恶性皮肤病变、炎症性皮肤病以及局部细菌和真菌感染。我们的概念是基于最近发现的一系列分子，这些分子在各种条件下都显示出非凡的敏化单线态氧的能力。可见光吸收光敏剂在以前的工作中已经被证明没有暗毒性。我们的初步体外工作也表明，它可以内化到小鼠癌细胞系和革兰氏阳性细菌中，在照射后观察到显著的光毒性。它很容易被有机合成方法“定制”，这有可能导致一个用于不同应用的PS组合库。在将PS局部应用于受影响区域之后，经过一段时间的潜伏期，该区域被适当波长和强度的光选择性地照射。这通过纳米结构PS对分子氧的催化作用而导致活性氧物种(ROS)的形成。ROS会导致受影响细胞丧失活力。

DESCRIPTION (provided by applicant): The objective of this proposal is to synthesize and evaluate novel, carbon-based nanostructure photosensitizers (PS) for the topical treatment of a variety of non-melanoma, pre-malignant and malignant cutaneous lesions, inflammatory dermatoses, and localized bacterial and fungal infections by topical photodynamic therapy (PDT). Our concept is based on a recently discovered family of molecules that have shown a remarkable ability to sensitize singlet oxygen under a variety of conditions. The visible light-absorbing photosensitizer has been shown in previous work to exhibit no dark toxicity. It has also been shown by our preliminary in vitro work to be internalized into a murine cancer cell line and a gram-positive bacterium where significant phototoxicity was observed upon irradiation. It is easily "tailored" by the methods of organic synthesis, which has the potential of leading to a combinatorial library of PS for different applications. After topical application of the PS to the affected area followed by a period of incubation, the area is selectively irradiated with light of appropriate wavelength and intensity. This causes the formation of reactive oxygen species (ROS) by the catalytic action of the nanostructure PS on molecular oxygen. The ROS cause a loss of viability in the affected cells.