Biofunctional Polymers for Intracellular Drug Delivery

描述(申请人提供)：这项建议的目标是开发方法，以加强基于核酸的治疗药物输送到非霍奇金淋巴瘤(NHL)细胞内的靶点。该项目将利用新型的pH敏感的“智能聚合物”载体来穿透限制进入细胞质和核间的内体屏障，在那里反义ODN和siRNA发挥其基因沉默作用。我们相信siRNA和AS-ODN在治疗非霍奇金淋巴瘤方面有很大的潜力，并假设递送方法的改进将促进它们在临床上的成功。这个项目旨在为生物分子药物开发新的药物输送系统，这些药物必须达到细胞内的疗效目标。SiRNA、反义寡核苷酸(ODN)和蛋白质等生物疗法具有巨大的治疗潜力，但有效地形成和传递它们仍然是一个被广泛认识的挑战。在这里，我们将开发用于siRNA药物的智能聚合物载体，这种载体可能被广泛用于其他DNA、RNA和蛋白质药物。

DESCRIPTION (provided by applicant): The objective of this proposal is to develop approaches to enhance the delivery of nucleic acid based therapeutics to intracellular targets in Non-Hodgkin Lymphoma (NHL) cells. The project will utilize novel pH-sensitive "smart polymer" based carriers to penetrate the endosomal barrier that limits entry to the cytoplasmic and nuclear compartments where antisense-ODN and siRNA exert their gene silencing effects. We believe that siRNA and AS-ODN have great potential for the treatment of NHL and hypothesize that improvement in delivery methods will facilitate their success in the clinical setting. PUBLIC HEALTH REVELANCE This project aims to develop new drug delivery systems for biomolecular drugs that must reach intracellular targets for efficacy. Biotherapeutics such as siRNA, antisense oligonucleotides (ODN), and proteins have significant therapeutic potential, but effectively formulating and delivering them remains a widely recognized challenge. Here we will develop smart polymeric carriers for siRNA drugs, and such carriers might be used widely for other DNA, RNA, and protein drugs.