Abdelhamid Muhammad Sami, Wadan Al-Hassan Soliman, Saad Hager Adel, El-Dakroury Walaa A, Hageen Ahmed W, Mohammed Deyaa H, Mourad Sohaila, Mohammed Osama A, Abdel-Reheim Mustafa Ahmed, Doghish Ahmed S
Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, 11231, Cairo, Egypt.
Oral Biology Department, Faculty of Dentistry, Galala University, Galala Plateau, Attaka, 15888, Suez Governorate, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 18. doi: 10.1007/s00210-024-03764-7.
Antibody-drug conjugates (ADCs) have emerged as a promising strategy in targeted cancer therapy, enabling the precise delivery of cytotoxic agents to tumor sites while minimizing systemic toxicity. However, traditional ADCs face significant limitations, including restricted drug loading capacity, where an optimal drug-to-antibody ratio (DAR) is crucial; low DARs may lead to insufficient potency, while high DARs can cause rapid clearance and increased toxicity. Additionally, ADCs often suffer from instability in circulation due to the potential for premature release of cytotoxic agents, resulting in off-target effects and reduced therapeutic efficacy. Furthermore, their large size can impede adequate penetration into solid tumors, particularly in heterogeneous environments with varying antigen expressions. This review explores the innovative use of nanoparticles as carriers for ADCs, which offers a multifaceted approach to enhance therapeutic efficacy. By leveraging the unique properties of nanoparticles, such as their small size and ability to exploit the enhanced permeability and retention (EPR) effect, researchers can improve drug stability, prolong circulation time, and achieve more effective tumor targeting. Recent studies demonstrate that nanoparticle-encapsulated ADCs can significantly enhance treatment outcomes while reducing off-target effects, as evidenced by improved targeting capabilities and reduced toxicity in preclinical models. Despite the promising advancements, challenges remain, including potential nanoparticle toxicity and manufacturing complexities. This review aims to provide a comprehensive overview of the current research on nanoparticle-encapsulated ADCs. It highlights their potential to transform cancer treatment and offers insights into future directions for optimizing these advanced therapeutic strategies.
抗体药物偶联物(ADCs)已成为靶向癌症治疗中一种很有前景的策略,能够将细胞毒性药物精确递送至肿瘤部位,同时将全身毒性降至最低。然而,传统的ADC面临着重大限制,包括药物负载能力受限,其中最佳药物与抗体比率(DAR)至关重要;低DAR可能导致效力不足,而高DAR可能导致快速清除和毒性增加。此外,由于细胞毒性药物可能过早释放,ADCs在循环中往往不稳定,从而导致脱靶效应和治疗效果降低。此外,它们的大尺寸会阻碍其充分渗透到实体瘤中,尤其是在抗原表达各异的异质环境中。这篇综述探讨了纳米颗粒作为ADCs载体的创新应用,这提供了一种多方面的方法来提高治疗效果。通过利用纳米颗粒的独特性质,如它们的小尺寸以及利用增强的渗透和滞留(EPR)效应的能力,研究人员可以提高药物稳定性、延长循环时间并实现更有效的肿瘤靶向。最近的研究表明,纳米颗粒包裹的ADCs可以显著提高治疗效果,同时减少脱靶效应,临床前模型中的靶向能力提高和毒性降低证明了这一点。尽管取得了有前景的进展,但挑战依然存在,包括潜在的纳米颗粒毒性和制造复杂性。这篇综述旨在全面概述目前关于纳米颗粒包裹的ADCs的研究。它强调了它们在改变癌症治疗方面的潜力,并为优化这些先进治疗策略的未来方向提供了见解。