Noncationic polymer-assisted carrier for nucleic acid drug delivery

非阳离子聚合物辅助的核酸药物载体

Nucleic acid drugs are emerging as a novel biotherapeutic modality for disease treatment,targeting nucleic acids to regulate the protein translation process and thereby facilitating disease management.They hold significant promise in biomedical applications and treatment avenues.Given their negative charge,high molecular weight,and hydrophilic properties,nucleic acid drugs require carriers to traverse multiple biological barriers and facilitate intracellular delivery.Cationic material-based carriers present an unprecedented opportunity to address these challenges through electrostatic interactions with nucleic acids.However,concerns regarding the biosafety and cytotoxic responses of cationic materials have emerged in early clinical studies.As a result,the use of non-cationic polymer carriers,by controlling or circumventing the use of cationic materials,represents a promising approach for nucleic acid delivery.In this review,we highlight various designs of non-cationic polymer carriers that go beyond the principle of electrostatic interactions,including conjugation,chemical bonding,physical crosslinking,hydrophobic interactions,and coordination bonding with nucleic acids.Additionally,we discuss strategies for enhancing the efficiency of nucleic acid delivery and therapeutic effects of non-cationic polymer carriers,focusing on targeted delivery,cellular internalization,and endosomal escape.

核酸药物作为疾病治疗过程中一类新的生物治疗方式,以核酸为靶标,通过对蛋白翻译过程的调控,实现疾病治疗,在生物医学应用和治疗领域呈现出巨大的前景.由于核酸类药物具有负电荷、高分子量和亲水性等特性,因此需要载体来克服多种生物屏障,以促进其在细胞内的递送.基于阳离子材料的载体通过与核酸的静电相互作用,提供了前所未有的机会来应对这些挑战.然而,阳离子材料的生物安全性和细胞毒性反应一直是早期临床研究的主要难题.鉴于对阳离子材料的使用进行了控制或规避,非阳离子聚合物载体成为了核酸递送的杰出选择.在本综述中,我们重点介绍了各种非阳离子聚合物载体的设计原则,包括共轭、化学键、物理交联、疏水相互作用以及与核酸的配位键等,以深入探讨除静电相互作用外的其他递送机制.此外,我们还探讨了如何通过靶向递送、细胞内摄取和内体逃逸等策略来提高非阳离子聚合物载体的核酸递送效率和治疗效果.