Biomacromolecules. 2023 Aug 14;24(8):3638-3646. doi: 10.1021/acs.biomac.3c00385. Epub 2023 Jul 21.
Antibody drug conjugates (ADCs) are poised to have an enormous impact on targeted nanomedicine, especially in many cancer pathologies. The reach of the current format of ADCs is limited by their low drug-to-antibody ratio (DAR) because of the associated physiochemical instabilities. Here, we design antibody polymer conjugates (APCs) as a modular strategy to utilize polymers to address ADC's shortcomings. We show here that conjugation of polymer-based therapeutic molecules to antibodies helps increase the DAR, owing to the hydrophilic comonomer in the polymer that helps in masking the increased hydrophobicity caused by high drug loading. We show that the platform exhibits cell targetability and selective cell killing in multiple cell lines expressing disease-relevant antigens, ., HER2 and EGFR. The ability to use different functionalities in the drug as the handle for polymer attachment further demonstrates the platform nature of APCs. The findings here could serve as an alternative design strategy for the next generation of active targeted nanomedicine.
抗体药物偶联物 (ADC) 有望对靶向纳米医学产生巨大影响，特别是在许多癌症病理中。由于相关的物理化学不稳定性，当前 ADC 形式的应用范围受到其低药物抗体比 (DAR) 的限制。在这里，我们设计抗体聚合物偶联物 (APC) 作为一种利用聚合物解决 ADC 缺点的模块化策略。我们在这里表明，将基于聚合物的治疗分子与抗体偶联有助于提高 DAR，这要归功于聚合物中的亲水性共聚单体，它有助于掩盖由于高药物载量引起的增加的疏水性。我们表明，该平台在表达疾病相关抗原的多种细胞系中表现出细胞靶向性和选择性细胞杀伤性，例如 HER2 和 EGFR。能够在药物中使用不同的功能作为聚合物附着的把手进一步证明了 APC 的平台性质。这里的发现可以作为下一代主动靶向纳米医学的替代设计策略。
