Controlling Structure and Function of Polymer-Nanoparticle Assemblies for Health Applications

治疗疾病是所有加拿大人都面临的紧迫挑战。未来治疗各种疾病的关键是使现有药物更安全、更有针对性。靶向药物递送涉及药物与抗体或纳米颗粒的配方，以促进其针对身体的特定区域（例如癌性肿瘤），以使它们更有效，副作用更少。聚合物纳米粒子是一种高度稳定、生物相容性好、可生物降解的药物传递系统，能够封装多种治疗剂，包括药物、金纳米粒子（GNPs）和DNA，为治疗性纳米材料（纳米药物）开辟了令人兴奋的机会。在这项提案中，我们将利用我们在纳米颗粒聚合物功能化和微流控合成聚合物纳米颗粒方面的独特专业知识，以及HQP培训机会和CREATE项目（用于药物输送的聚合物纳米颗粒）所带来的合作，以解决当前聚合物纳米药物的研究挑战，从而开发出令人兴奋的疾病治疗新策略。例如，我们将设计一个基于聚合物的纳米平台，用于同时将抗癌药物和GNPs（增强辐射剂量）输送到癌性肿瘤中，以实现靶向和强大的联合治疗。本工作还将探索一种将DNA包装在聚合物纳米颗粒中用于基因治疗的新方法。这种方法将在分娩前更好地保护敏感的遗传物质，并在分娩后选择性光触发释放，从而实现基因/药物联合治疗，其中选择性基因表达增加了癌症对药物的敏感性，从而获得更好的总体患者结果。

The treatment of disease is a pressing challenge that touches all Canadians. A vital key to the future of treating all forms of disease is making existing drugs safer and more specific. Targeted drug delivery involves the formulation of drugs with antibodies or nanoparticles to promote their targeting to specific regions of the body (e.g. cancerous tumors), in order to make them more effective with fewer side effects. Polymer nanoparticles are widely studied drug delivery systems which can be highly stable, biocompatible, biodegradable, and capable of encapsulating multiple therapeutic agents, including drugs, gold nanoparticles (GNPs), and DNA, opening up exciting opportunities for therapeutic nanomaterials (nanomedicines). In this proposal, we leverage our unique combined expertise in polymer functionalization of nanoparticles and microfluidic controlled synthesis of polymer nanoparticles, in addition to HQP training opportunities and collaborations enabled by the CREATE program Polymer Nanoparticles for Drug Delivery (PoND), in order to address current research challenges in polymer-based nanomedicines and thus develop exciting new strategies for disease treatment. For example, we will design a single polymer-based nanoplatform for delivering both an anticancer drug and GNPs (which enhance radiation doses) to cancerous tumors at the same time for targeted and powerful combination therapy. This work will also explore a new way of packaging DNA in polymer nanoparticles for gene therapy applications. This approach will provide better protection of the sensitive genetic material before delivery along with selective light-triggered release after delivery, enabling combined gene/drug treatments where selective gene expression increases the cancer sensitivity to the drug for a better overall patient outcome.