具有近红外释药响应的免疫脂质体的制备及其性能研究

Well known as a good drug carrier, especially for the antitumor drugs, immunoliposomes have attracted increasing attention due to its ability to reduce the toxicity of carried drugs, to deliver drugs to the target tissue or cells, and to encapsulate the drug molecules efficiently. How to improve the controllability of drug release from immunoliposomes is currently an attractive and challenging question for all the researchers in this field. Manual control of the drug release is the best way to deliver drugs to the right target precisely, which requires that liposomes can make a right drug-release response to external signals. Near infrared (Near-IR) can penetrate relatively deep into biological soft tissues without any obvious damage to the normal cells. Therefore, loading of the gold nanorods (GNRs), which has a special photothermal response to Near-IR, into the thermosensitive immunoliposome will make it an ideal drug carrier, which can achieve a targeted drug delivery precisely in vivo. This project focuses on the design and assembling of this particular kind of functional immunoliposomes, together with the characterization of their physicochemical properties and drug release behavior. This project includes: 1) Preparation and modification of gold nanorods, and then loading it into the liposome; 2) Determination of the liposomal composition and adjusting the ratio in order to achieve the goal of the immune targeting, a reliable stability, a higher releasing temperature, and a good encapsulation performance; 3) The overall evaluation of the photothermal-controlled drug release system triggered by the Near-IR light. Based on the research experiences of the applicant, the design and assembling of this particular functional immunoliposome with gold nanorods loaded is theoretically feasible and financially affordable.

免疫脂质体作为药物载体，具有生物毒性小、靶向性高、包埋性能好等优点。如何提高免疫脂质体的释药可控性，是目前国际同行研究的热点和难点。人为控制释药时机是实现精确给药的最佳手段，这要求脂质体能对外来信号作出正确的释药反应。近红外光具有组织穿透力强，对正常细胞破坏性小的特点，因此把具有近红外光热效应的金纳米棒装载到热敏性免疫脂质体中，将成为一种理想的药物载体，真正实现脂质体在体内的精确靶向给药。本课题将致力于设计组装这种功能化的免疫脂质体，并研究其物理化学性质和释药性能。研究内容包括：1）金纳米棒的制备、修饰及在脂质体内的装载；2）确定脂质体的组成并对其配比进行优化，使其具有抗体靶向性、稳定性好、热敏温度高、包封性能好等特点；3）近红外光热效应对脂质体内小分子释放效果的综合评估。基于申请人多年的相关研究工作和经验，实现这种功能脂质体的设计和对金纳米棒的装载在理论方法和成本控制上都是现实可行的。

免疫脂质体作为药物载体，具有生物毒性小、靶向性高、包埋性能好等优点。如何提高免疫脂质体的释药可控性，是目前国际同行研究的热点和难点。人为控制释药时机是实现精确给药的最佳手段，这要求脂质体能对外来信号作出正确的释药反应。近红外光具有组织穿透力强，对正常细胞破坏性小的特点，因此把具有近红外光热效应的金纳米棒等纳米材料装载到热敏性免疫脂质体中，将成为一种理想的药物载体，真正实现脂质体在体内的精确靶向给药。本课题的研究目标在于设计制备一种具有特殊近红外光响应的免疫脂质体,以实现对药物小分子的可控释放。本项目主要围绕具有近红外光热效应的金纳米粒子的制备、修饰、脂质体装载及性能表征展开。研究过程中发现要将具有近外光热效应的金纳米棒装载入脂质体中存在很大困难，因此在不放弃该方向尝试的同时，我们把研究重心调整为对具有近红外光热效应的金纳米材料的表面改性，以改善其生物毒性、提高其光热效应和稳定性。此外我们还对另外一些具有近红外光热效应的纳米材料，比如PEDOT进行了装载尝试。