PLGA-based nanomedicines for cancer therapy: From synthesis and surface functionalization to clinical translation

Abstract

Cancer remains a leading cause of global mortality, underscoring the urgent need for innovative, precise therapeutic strategies. Conventional modalities, particularly systemic chemotherapy and radiotherapy, are often limited by restricted bioavailability, high systemic toxicity, and poor tumor specificity, which collectively compromise clinical efficacy. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles have long been a cornerstone of biomedical engineering, distinguished by their superior biodegradability, biocompatibility, and tunable physicochemical properties. These versatile carriers enable the encapsulation of diverse therapeutic agents, protecting them from premature degradation and leveraging the enhanced permeability and retention effect to maximize intratumoral accumulation. This review critically examines recent advances in synthesis methodologies, including electrospray and microfluidics, which have significantly optimized drug-loading efficiency and release kinetics. Furthermore, we highlight innovations in surface engineering, focusing on hybrid material integration and ligand conjugation strategies designed to enhance active targeting precision while minimizing off-target adverse effects. Additionally, emerging research on the co-delivery of multiple agents to foster synergistic outcomes and combat multidrug resistance is explored. Despite the growing number of clinically approved formulations, challenges with residual organic solvents, incomplete release, and deep-tissue penetration persist. Consequently, this review outlines future perspectives on optimizing PLGA formulations to overcome these limitations, with the ultimate goal of expanding their therapeutic utility beyond oncology into broader biomedical applications.