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.
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