Proteins and peptides have played a pivotal role in revolutionizing disease treatment over the last century. Despite their commercial success, protein therapeutics can be eliminated or inactivated in the body excretion or other metabolic pathways. Polymeric materials have been used to stabilize these biomolecules in the presence of external stressors as excipients, conjugates, and in nanomaterial formulations. Numerous advantages arise from the combination of therapeutic agents with polymeric carriers, including improved stability, solubility, prolonged blood circulation, and reduced immunogenicity. PEGylation, the covalent conjugation of poly(ethylene glycol) to a biomolecule of interest, is a common technique that has been employed in 31 FDA-approved therapeutic protein formulations to date. Although PEGylation has been widely adopted, there have been numerous advancements in the protein stabilization field using a variety of polymers including, but not limited to, poly(oxazolines), polypeptides, zwitterionic polymers, and polysaccharides with additional beneficial properties such as biocompatibility and biodegradability. Polymeric carriers can also protect lyophilized protein-peptide products from the stresses of supercooling, ice crystallization, sublimation, and desorption. This review discusses recent progress on the design principles of polymeric tools for biomolecule stabilization and delivery, with a focus on conjugates and nanomaterials. The clinical status of these materials and current challenges impeding the clinical translation are presented. In addition, various future possibilities for polymeric-protein therapies are also highlighted. Finally, the current computational landscape that harnesses the tools of machine learning combined with experimental validation to design polymeric systems tailored for biomolecule stability are discussed.

中文翻译：

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聚合物介导的蛋白质/肽治疗稳定性：当前进展和未来方向


蛋白质和肽在上个世纪的疾病治疗革命中发挥了关键作用。尽管蛋白质疗法在商业上取得了成功，但它们可以在体内排泄或其他代谢途径中被消除或失活。聚合物材料已被用作赋形剂、缀合物和纳米材料制剂，用于在外部应激源存在的情况下稳定这些生物分子。治疗剂与聚合物载体的组合产生了许多优点，包括改善的稳定性、溶解度、延长的血液循环和降低的免疫原性。聚乙二醇化（聚乙二醇）与目标生物分子的共价结合是一种常用技术，迄今为止已用于 31 种经 FDA 批准的治疗性蛋白质制剂。尽管聚乙二醇化已被广泛采用，但使用各种聚合物（包括但不限于聚恶唑啉）、多肽、两性离子聚合物和具有生物相容性和生物降解性等其他有益特性的多糖，在蛋白质稳定领域取得了许多进展。聚合物载体还可以保护冻干蛋白肽产品免受过冷、冰结晶、升华和解吸的影响。本综述讨论了用于生物分子稳定和递送的聚合物工具的设计原理的最新进展，重点是缀合物和纳米材料。介绍了这些材料的临床状况以及当前阻碍临床转化的挑战。此外，还强调了聚合物蛋白疗法的各种未来可能性。 最后，讨论了当前利用机器学习工具与实验验证相结合来设计针对生物分子稳定性的聚合物系统的计算前景。