Biofunctional Polymers for Intracellular Drug Delivery

描述（由申请人提供）：本提案的目的是开发增强基于核酸的治疗剂向非霍奇金淋巴瘤（NHL）细胞中的细胞内靶点递送的方法。该项目将利用新型pH敏感的“智能聚合物”载体来穿透限制进入细胞质和核隔室的内体屏障，反义ODN和siRNA在细胞质和核隔室中发挥其基因沉默作用。我们相信siRNA和AS-ODN在NHL的治疗中具有巨大的潜力，并假设递送方法的改进将促进它们在临床环境中的成功。该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靶点才能发挥功效。生物治疗剂如siRNA、反义寡核苷酸（ODN）和蛋白质具有显著的治疗潜力，但有效地配制和递送它们仍然是广泛认识到的挑战。本文将为siRNA药物开发智能聚合物载体，并将其广泛应用于其他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.