Dixit Tanu, Aswini Annamraju, Nikam Harshal, Vaidya Anuradha, Ravindran Selvan
Faculty of Medical and Health Sciences, Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Lavale, Pune, 412 115, India.
Serum Institute of India Private Limited, Pune, India.
Discov Nano. 2025 Aug 18;20(1):139. doi: 10.1186/s11671-025-04303-w.
Antibody-drug conjugates (ADCs) and antibody-conjugated nanoparticles (ACNPs) are targeted therapies achieved by combining monoclonal antibodies (mAbs) with cytotoxic payloads or nanocarriers. ADCs consist of mAbs conjugated to the cytotoxic payloads via a linker, thus enabling tumor-specific delivery and reducing systemic toxicity. ACNPs add to this targeted therapeutic window by using nanoparticles. This conjugation promotes controlled drug release, higher drug-to-antibody ratios (DAR), and reduced off-target effects. ADCs exhibit precision in cell killing but face limitations such as antigen heterogeneity and Fc-mediated sequestration, whereas ACNPs enhance payload capacity and tumor penetration through their tunable physicochemical properties. ACNPs also facilitate multivalent binding by functionalizing multiple antibody molecules on their surface, improving target cell recognition and binding strength. Recent advancements include 14 FDA-approved ADCs and ACNPs in Phase I/II trials. A critical analysis of synthesis methods reveals that site-specific conjugation techniques enhance batch consistency, while characterization technologies, such as SEC-HPLC, LC-MS/MS, and SPR, address challenges related to DAR quantification and aggregation. Linker chemistry innovations, such as PEGylated maleimides balancing hydrophilicity and stability, are highlighted alongside emerging payloads. Despite progress, both platforms face translational hurdles: ADCs contend with manufacturing complexity and resistance mechanisms, while ACNPs require standardized in vitro models to predict in vivo behavior. This review emphasizes the significance of comparative efficacy studies and strategies for optimizing antibody density and orientation on nanoparticles. Together, these insights connect the gaps between synthesis, characterization, and therapeutic outcomes, steering the future development of targeted bioconjugates.
抗体药物偶联物（ADCs）和抗体偶联纳米颗粒（ACNPs）是通过将单克隆抗体（mAbs）与细胞毒性载荷或纳米载体相结合而实现的靶向治疗方法。ADCs由通过连接子与细胞毒性载荷偶联的单克隆抗体组成，从而实现肿瘤特异性递送并降低全身毒性。ACNPs通过使用纳米颗粒扩展了这一靶向治疗范围。这种偶联促进了药物的可控释放、更高的药物与抗体比率（DAR）以及减少脱靶效应。ADCs在细胞杀伤方面表现出精准性，但面临抗原异质性和Fc介导的隔离等局限性，而ACNPs通过其可调节的物理化学性质提高了载荷容量和肿瘤穿透性。ACNPs还通过在其表面功能化多个抗体分子促进多价结合，提高靶细胞识别和结合强度。最近的进展包括14种已获美国食品药品监督管理局（FDA）批准的ADCs以及处于I/II期试验的ACNPs。对合成方法的批判性分析表明，位点特异性偶联技术提高了批次一致性，而诸如尺寸排阻色谱 - 高效液相色谱（SEC - HPLC）、液相色谱 - 串联质谱（LC - MS/MS）和表面等离子体共振（SPR）等表征技术解决了与DAR定量和聚集相关的挑战。同时还强调了连接子化学创新，如平衡亲水性和稳定性的聚乙二醇化马来酰亚胺，以及新兴的载荷。尽管取得了进展，但这两个平台都面临转化障碍：ADCs面临制造复杂性和耐药机制问题，而ACNPs需要标准化的体外模型来预测体内行为。本综述强调了比较疗效研究以及优化纳米颗粒上抗体密度和取向策略的重要性。这些见解共同填补了合成、表征和治疗结果之间的差距，引领靶向生物偶联物的未来发展。
