基于上转换发光技术的光动力治疗纳米载体系统的构建

光动力疗法与手术、化疗、放疗相比，具有创伤小、毒性低、无痛苦等显著的优势，对实现治愈癌症具有重要意义。然而，该方法存在光敏剂亲水性差、无肿瘤靶向能力，可见光激发穿透深度浅、易造成组织烧伤等缺陷。本项目针对上述缺陷，拟设计构建以近红外光激发上转换纳米颗粒为能量供体，传统光敏剂为能量受体，叶酸修饰的高分子脂质体为保护壳层的"无机-有机核壳纳米药物载体"。其中，叶酸修饰的高分子脂质体壳层可有效提高光敏剂亲水性和肿瘤靶向性；近红外光激发上转换纳米颗粒，不仅有效提高穿透深度，减少组织烧伤，而且具有荧光体内成像作用。在此基础上，通过体内外实验，深入探讨纳米药物载体激发光敏剂产生单线态氧杀伤肿瘤的机理，系统验证该载体系统对肿瘤杀伤的实际功效，最终筛选出稳定性强、适用性广、杀伤肿瘤效率高的核壳纳米药物载体。本项目可为拓宽纳米药物载体的构建思路，解决光动力疗法的缺陷，研制新一代光动力制剂提供重要科学依据。

Compared with surgery, chemotherapy and actinotheraphy, photodynamic therapy (PDT) has some unique advantages, such as lower operative damage, lower toxicity and less pain, which makes it as one of the most important method for cancer treatment. Nevertheless the efficiency of PDT is limited due to the hydrophobic nature of photosensitizer, low tumor selectivity functions and low penetration depth of the excitation light source. In this proposal, based on near-infrared excitation technique and polymeric liposome technique, a highly efficient multifunctional nanoplatform for PDT is designed on the basis of energy transfer from multicolor luminescent upconversion nanoparticles (UCNPs) to photosensitizers (PS). The relation between the cancer treatment effect and the singlet oxygen produced by photosensitiser will be studied closely. The final purpose is to optimize all these parameters to get the core-shell nanocarrier with good stability, wide applicability and high cancer treatment efficiency. This study will be of great significance to expand ideas for the drug carrier deigns, deal with the problems of currently PDT and develop the new generation of photodynamic drugs.