Engineering intelligent PLGA nanoparticles for site-specific delivery

药物研究中的一个基本探索是开发可以选择性靶向某些细胞的药物递送方法，同时限制周围健康细胞暴露于药物以避免附带损害。纳米颗粒（NPs）的进步正在迅速发展，并为药物递送提供了令人兴奋的前景。聚合物纳米颗粒，我主要关注的递送系统，是药物递送的通用平台，因为它们具有合适的大小以被细胞吸收，具有可以物理或化学修饰的大表面积，并且与其他药物递送系统相比具有优异的安全性记录。 我的研究将通过修饰纳米粒子的表面来进行生物工程，然后研究这些修饰如何影响它们的靶向效率。具体来说，我的目标是：1）探索设计一系列能够靶向特定细胞的修饰纳米粒子的方法，2）根据它们的行为选择适合靶向药物递送的候选物，3）在细胞培养物和动物（小鼠）模型中测试这些候选物的效率和毒性，以及4）绘制体内组织分布图。该基础研究计划将设计一个有效的靶向递送系统，了解NP结构和活性之间的详细关系，并解决有关NP结构和化学的基本要求的关键问题，以选择性地靶向细胞/组织上的特定标志物。参加这项研究的学生将获得专业知识和技能，这将有助于他们在学术界，制药业或生物技术实验室未来的就业。从长远来看，这项工作将为治疗动物和人类的先天性和后天性疾病提供基础并最终导致治疗。

One fundamental quest in pharmaceutical research is developing methods of drug delivery that can selectively target certain cells, while limiting exposure of surrounding healthy cells to the drug to avoid collateral damage. Advancements in nanoparticles (NPs) are rapidly progressing and offer exciting promise for drug delivery. Polymeric NPs, the delivery system I primarily focus upon, are versatile platforms for drug delivery as they are of appropriate size to be taken up by cells, have a large surface area that can be physically or chemically modified, and an excellent record of safety compared to other drug delivery systems. My research will bioengineer NPs by modifying their surface, then investigate how these modifications affect their targeting efficiency. Specifically, my objectives are to: 1) explore approaches to engineer a series of modified NPs that are able to target specific cells, 2) select candidates suitable for targeted drug delivery based on their behaviour, 3) test these candidates for efficiency and toxicity in cell cultures and in an animal (mouse) model, and 4) map tissue distribution in the body. This basic research program will engineer an efficient targeted delivery system, develop an understanding of the detailed relationship between NP structure and activity, and address key questions regarding the fundamental requirements of NP structure and chemistry to selectively target specific markers on cells/tissues. Students participating in this research will gain expertise and skills that will serve them well in future employment in academia, the pharmaceutical industry, or biotechnology laboratories. In the long term, this work will provide the basis for and eventually lead to the treatment of innate and acquired diseases in animals and humans.