基于上转换纳米粒的深层肿瘤光动力学治疗量效关系的基础研究

项目名称： 基于上转换纳米粒的深层肿瘤光动力学治疗量效关系的基础研究

项目编号： No.61335007

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 无线电电子学、电信技术

项目作者： 顾月清

作者单位： 中国药科大学

项目金额： 260万元

中文摘要： 光动力治疗PDT以其光照强度、时间、范围等可控性可实现肿瘤病灶的定时定位定量治疗，但传统PDT由于其激发光的组织穿透能力弱而不能进行深层病灶的治疗；上转换纳米粒具有将较深组织穿透力的近红外光转变成可见光的能力，为深层肿瘤PDT提供了可能。但基于上转换机制的PDT研究刚刚起步，许多量效关系及成药前景尚不明确。本项目拟在实验室工作基础上,进一步合成并优化上转换纳米粒发光特性，通过智能壳聚糖胶束包裹上转换纳米粒及两种匹配的光敏剂而构建能量转移系统，评价其成药前景，重点考察各量效关系（激光能量、照射时间及频率、复合物浓度、组织深度、活性氧产量等）建立数学模型以指导深层PDT。同时，通过光可控壳聚糖胶束的崩解，优化上转换纳米粒、光敏剂及氧分子间能量转移特性使PDT活性氧最优。进一步，将抗肿瘤药物同时载入壳聚糖复合载体中，由近红外光触发光敏纳米胶束的定时释放，在时序上实现先光动力治疗后化疗的联合作用。

中文关键词： 上转换纳米粒;光动力学治疗;智能壳聚糖纳米胶束;量效关系;深层肿瘤

英文摘要： Featured with the merits of controllable in laser intensity, irradiation time and areas, photodynamic therapy(PDT) possess the capability of quantitative tumor therapy in designated time and specific pathological location. However, the tradition PDT is unable to perform the therapy in the site of deep tissue due to the limited penetration depth of the irradiation light on the living tissue. Upconversion nanoparticles (UCNP), with the ability of conversing the absorbed near-infrared light to visible light to trigger the surrounding photosensitizers, provide the possibility of deep tumor PDT. Unfortunately, upconversion nanoparticles-based PDT is in its initial stage, the dose-effect relationship and other properties serving as drug are unclear, which is the aim of this project. In this proposed work, we will firstly synthesize and optimize the conversional optical properties of our rare earth nanopartilces to math the traditional photosensitizers. Then, we will build an energy transfer PDT system by entrapping the UCNP and two matched photosensitizers into the high payload chitosan micells. The promising of the PDT system as feasible drug carrier will be evaluated. We will place our emphasis on the dose-effect relationship including the energy density of the light, irradiation time and periods, concentration of the UCNP-photosensitizer compound, depth of the tissue, production of reactive oxygen, to establish a mathematic model to guide the real PDT in deep tissue. Furthermore, we will investigate the combined efficacy of PDT with chemotherapy by uploading the anticancer drug into the NIR triggered chitosan micells based PDT system.

英文关键词： upconversion nanoparticle;photodynamic therapy;smart chitosan micelles;dose-effect relationship;deep seated tumor