Development of long-circulating nanoparticles for targeted drug delivery applications

聚合物纳米颗粒是靶向给药应用的一个很有前途的平台。体内给药的中心挑战在于肝和脾快速清除体内循环中的微粒。结果，只有一小部分给药的纳米颗粒剂量能够到达目标病变细胞和组织。当血浆蛋白结合到颗粒表面，使巨噬细胞看到它们时，纳米颗粒的清除过程就开始了。拟议拨款的中心目标是建立一个积极的研究计划，以开发能够有效地将血浆蛋白在颗粒表面的吸附降至最低的载药聚合物纳米颗粒。据推测，通过系统地优化聚合物纳米颗粒的表面性质，可以显著降低巨噬细胞清除纳米颗粒的速度。我们的策略包括用天然聚合物来修饰颗粒表面，这种聚合物模仿入侵病原体的蛋白质排斥表面特性。在拟议的五年研究计划的第一阶段，将开发一种平台技术，用于合成用于靶向药物输送的自组装聚合物纳米颗粒。该计划的第二阶段将专注于控制纳米颗粒的物理化学性质，以最大限度地减少蛋白质在颗粒表面的吸附。根据提议的计划开发的纳米颗粒可用于各种临床和生物医学应用。人们普遍认为，靶向给药在药物创新中具有很大的前景，因为它能够提高现有药物的有效性，降低手术和住院的必要性和成本，并提高患者的生活质量。拟议的NSERC发现拨款的成功完成将有助于确保加拿大在纳米生物技术和靶向药物输送方面的地位。

Polymeric nanoparticles represent a promising platform for targeted drug delivery applications. The central challenge in administering polymeric nanoparticles in vivo lies in the rapid particle clearance from the systemic circulation by the liver and spleen. As a result, only a small fraction of the administered nanoparticle dose is able to reach the targeted diseased cells and tissues. The nanoparticle clearance process is initiated when blood plasma proteins bind to the particle surface, making them visible to macrophages. The central aim of the proposed grant is to establish an active research program for developing drug-loaded polymeric nanoparticles that can effectively minimize plasma protein adsorption on the particle surface. It is hypothesized that the rate of nanoparticle clearance by macrophages can be substantially decreased by systemically optimizing the surface properties of polymeric nanoparticles. Our strategy involves modifying particle surfaces with natural polymers that mimic the protein-repelling surface properties of invasive pathogens. In the first phase of the proposed five-year research program, a platform technology will be developed for synthesizing self-assembled polymeric nanoparticles for targeted drug delivery. The second phase of the program will focusing on controlling the nanoparticle physicochemical properties to minimize protein adsorption on the particle surface. The nanoparticles developed from the proposed program may be used for a variety of clinical and biomedical applications. It is generally understood that targeted drug delivery holds great promise in pharmaceutical innovation for its ability to increase the effectiveness of existing drugs, decrease the necessity and thus cost for surgery and hospitalization and increase the quality of life of patients. The successful completion of the proposed NSERC discovery grant will help to secure Canada's position in nanobiotechnology and targeted drug delivery.