Forenzo Chloe, Arnold Noah, Larsen Jessica
Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, USA.
Department of Bioengineering, Clemson University, Clemson, SC, USA.
Nanomedicine (Lond). 2025 Sep;20(18):2357-2374. doi: 10.1080/17435889.2025.2542110. Epub 2025 Aug 5.
As the healthcare landscape rapidly evolves to include advanced drug delivery methods with better cellular targeting and more efficient delivery, polymeric nanocarriers have emerged to close translational gaps. Acting on the central dogma of molecular biology, mRNA and protein therapeutics can offer curative potential for various debilitating diseases. Considering these advancements, polymeric nanocarriers have been widely explored preclinically in delivering both proteins and mRNA for various disease therapies. This review introduces how the next generation of polymeric nanocarriers can be designed for protein therapeutics, including some advantages and disadvantages as well as specific design considerations for mRNA vs protein delivery. The evolution of these polymeric nanocarriers is then examined, and the current landscape and emerging trends are presented. Finally, we provide an outlook on the clinical translation of polymeric nanocarrier delivery of mRNA and proteins, including a future perspective for the field. Despite the preclinical promise of these delivery systems in both mRNA and protein constructs, clinical translation is underwhelming. Continued development of polymeric nanocarriers is underway and early clinical trials have provided a foothold into translation for this technology. A key challenge for polymeric nanomedicine is bridging the gap between promising preclinical data and successful clinical translation.
随着医疗保健领域迅速发展，纳入了具有更好细胞靶向性和更高递送效率的先进药物递送方法，聚合物纳米载体应运而生，以弥合转化差距。基于分子生物学的中心法则，信使核糖核酸（mRNA）和蛋白质疗法可为各种使人衰弱的疾病提供治愈潜力。鉴于这些进展，聚合物纳米载体已在临床前广泛用于递送蛋白质和mRNA以进行各种疾病治疗。本综述介绍了如何设计下一代用于蛋白质疗法的聚合物纳米载体，包括一些优缺点以及mRNA与蛋白质递送的具体设计考虑因素。接着考察了这些聚合物纳米载体的演变，并介绍了当前的情况和新趋势。最后，我们对聚合物纳米载体递送mRNA和蛋白质的临床转化进行了展望，包括该领域的未来前景。尽管这些递送系统在mRNA和蛋白质构建体的临床前研究中前景广阔，但临床转化情况并不理想。聚合物纳米载体的持续研发正在进行中，早期临床试验为该技术的转化提供了一个立足点。聚合物纳米医学面临的一个关键挑战是弥合有前景的临床前数据与成功的临床转化之间的差距。
