Engineering intelligent PLGA nanoparticles for site-specific delivery

制药研究的一个基本问题是开发药物递送方法，可以选择性地针对某些细胞，同时限制周围健康细胞接触药物，以避免附带损害。纳米颗粒（NPs）的进步正在迅速发展，并为药物输送提供了令人兴奋的前景。聚合物NPs，我主要关注的传递系统，是药物传递的通用平台，因为它们大小合适，可以被细胞吸收，具有可物理或化学修饰的大表面积，与其他药物传递系统相比，具有良好的安全性记录。我的研究将通过修饰NPs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NPs的方法；2)根据其行为选择适合靶向药物递送的候选药物；3)在细胞培养和动物（小鼠）模型中测试这些候选药物的效率和毒性；4)绘制体内组织分布。这个基础研究项目将设计一个有效的靶向递送系统，发展对NP结构和活性之间详细关系的理解，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/组织上的特定标记物。参与这项研究的学生将获得专业知识和技能，这些知识和技能将为他们未来在学术界、制药行业或生物技术实验室的就业提供很好的帮助。从长远来看，这项工作将为动物和人类的先天和获得性疾病的治疗提供基础，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.