Folate-modified chitosan nanocarriers in precision oncology: molecular engineering, targeted drug delivery, and clinical perspectives.

Cancer remains a major cause of morbidity and mortality worldwide, and the effectiveness of conventional chemotherapy is frequently limited by poor tumor selectivity, systemic toxicity, rapid drug clearance, and multidrug resistance. These limitations have accelerated the development of targeted nanocarrier systems, with folate-functionalized chitosan nanoparticles (NPs) emerging as promising platforms for precision cancer therapy. Chitosan possesses favorable biocompatibility, biodegradability, mucoadhesive properties, and chemical versatility, while folate conjugation enables active targeting through folate receptor (FR)-mediated endocytosis. As FRs are overexpressed in several malignancies, including breast, ovarian, lung, colorectal, pancreatic, and cervical cancers, folate-functionalized NPs have the potential to enhance selective drug delivery, improve tumor accumulation, and minimize off-target toxicity. Recent advancements in smart and multifunctional nanocarriers, including MXene quantum dot polymer nanocomposites, have further emphasized the importance of surface engineering, multifunctionality, controlled drug release, and safety evaluation in the development of next-generation targeted drug delivery systems. Folate-functionalized chitosan NPs represent a biologically relevant and versatile class of targeted nanocarriers, offering the potential to enhance cellular uptake, provide sustained and controlled drug release, improve anticancer efficacy, and reduce systemic toxicity compared with non-targeted formulations. Important translational challenges, including reproducibility, formulation stability, interpatient variability in FR expression, immunogenicity, scalability, and regulatory considerations, also require careful attention for successful clinical development. Overall, this review provides a comprehensive overview of the design, synthesis, functionalization, therapeutic applications, pharmacokinetics, biodistribution, safety profiles, and clinical translation potential of folate-functionalized chitosan NPs for precision cancer therapy.