兼具双光子成像功能和双光子光动力疗效的基于共轭高分子的纳米光敏材料的制备与研究

Photodynamic therapy is a novel minimally-invasive cancer therapy technique with less side effects. Two-photon excitation can further improve its biological penetration depth and 3-dimensional selectivity. To overcome the disadvantages of small two-photon absorption cross sections of traditional photosensitizers for photodynamic therapy and fluorophores for bio-imaging, here we propose development of novel conjugated polymer based nano-photosensitizers for simultaneous two-photon imaging and two-photon photodynamic therapy with enhanced t two-photon properties through energy transfer and plasmon resonance. Conjugated polymers have been known to possess large two-photon absorption cross sections due to their delocalized electronic structures. In these nanomaterials, two-photon excitation energy transfer from conjugated polymers to red-emitting fluorophores and photosensitizers will help to improve two-photon excitation fluorescence, singlet oxygen generation and photodynamic activity of these materials by up to hundreds or even thousands of times. We will further introduce noble metal nanoparticle into these nanomaterials to utilize the localized surface Plasmon resonance effects of noble metal nanoparticles to improve two-photon excitation efficiency of conjugated polymers, fluorescence yield of red-emitting fluorophores and energy transfer efficiency between them. These nanoparticles will be further surface-modified to render selective targeting the cancer cells. These nanoparticles could be utilized for two-photon imaging/detection of cancer cells and simultaneous two-photon photodynamic therapy treatment. Successful execution of this project is expected to provide highly efficient multifunctional nano-photosensitizers for two-photon photodynamic therapy, which will greatly foster the wide applications of this novel cancer therapy technique.

光动力疗法是一种低侵袭性、副作用少的新兴癌症疗法。双光子激发技术可更进一步改善其生物穿透性和三维选择性。为了克服传统光敏剂和生物成像分子的双光子吸收截面较小的弱点，本项目将发展兼具双光子成像功能和双光子光动力疗效的基于共轭高分子的纳米光敏材料，并通过能量传递和等离子共振来增强其性能。共轭高分子由于其离域电子结构而具高双光子吸收截面。在这些纳米材料中，共轭高分子到红光发色团或光敏剂的能量传递可提高这些材料在双光子激发条件下的红光发射强度、单线态氧产生及光动力疗效达几百倍至上千倍。我们进一步在这些纳米材料中引入贵金属纳米利用其等离子共振效应来增强高分子的双光子激发效率、发红光分子的荧光效率及能量传递效率。这些钠米材料可进行表面修饰使之能跟癌细胞选择性结合。这种纳米材料可用于双光子成像检测和同步治疗。该项目有望提供一种能用于双光子光动力疗法的高效多功能纳米光敏剂，大大推广此新兴癌症疗法的应用。

光动力疗法是一种低侵袭性、副作用少的新兴癌症疗法。双光子激发技术可更进一步改善其生物穿透性和三维选择性。为了克服传统光敏剂和生物成像分子的双光子吸收截面较小的弱点，本项目发展兼具双光子成像功能和双光子光动力疗效的基于共轭高分子的纳米光敏材料,并通过能量传递和等离子共振来进一步增强其性能。在本项目中，我们制备了两类兼具双光子红光发射和双光子光动力疗效的基于共轭高分子的纳米光敏材料：1）含共轭高分子+红光发光团+光敏剂的纳米复合材料；2）含贵金属纳米颗粒增强的共轭高分子+红光发光团+光敏剂的纳米复合材料两类。在这些纳米材料中，共轭高分子到红光发色团或光敏剂的能量传递可提高这些材料在双光子激发条件下的红光发射强度、单线态氧产生及光动力疗效达几百倍。我们进一步在这些纳米材料中引入贵金属纳米利用其等离子共振效应来增强高分子的双光子激发效率、发红光分子的荧光效率及能量传递效率。优化后的纳米复合光敏剂比原来的光敏剂的双光子荧光和双光子诱导单线态氧产量分别提高了980倍和792倍。这些钠米材料进一步进行表面修饰使之能跟癌细胞选择性结合，从而能够有选择性的识别并杀死癌细胞而不影响正常细胞。这种纳米材料可用于双光子成像检测和同步治疗，副作用少。该项目的结果提供了一类能用于双光子光动力疗法的高效多功能纳米光敏剂，有望大大推广此新兴癌症疗法的应用。