Polyglutamic acid in cancer nanomedicine: Advances in multifunctional delivery platforms

Polyglutamic acid (PGA)-coated nanoparticles have emerged as a significant advancement in cancer nanomedicine due to their biocompatibility, biodegradability, and versatility. PGA enhances the stability and bioavailability of therapeutic agents, enabling controlled and sustained drug release with reduced systemic toxicity. Stimuli-responsive modifications to PGA allow for precise drug delivery tailored to the tumor microenvironment, improving specificity and therapeutic outcomes. PGA's potential extends to gene delivery, where it facilitates safe and efficient transfection, addressing critical challenges such as multidrug resistance. Additionally, PGA-coated nanoparticles play a pivotal role in theranostic, integrating diagnostic and therapeutic capabilities within a single platform for real-time monitoring and treatment optimization. These nanoparticles have demonstrated enhanced efficacy in chemotherapy, immunotherapy, and combination regimens, tackling persistent issues like poor tumor penetration and non-specific drug distribution. Advancements in stimuli-responsive designs, ligand functionalization, and payload customization highlight the adaptability of PGA-based platforms for precision oncology. However, challenges such as scalability, stability under physiological conditions, and regulatory compliance remain key obstacles to clinical translation. This review explores the design, development, and applications of PGA-coated nanoparticles, emphasizing their potential to transform cancer treatment through safer, more effective, and personalized therapeutic approaches.