Advancements in single-chain antibody functionalized nanoparticles for the treatment of advanced solid tumors

Cancer therapeutics for solid tumors remain limited by the low specificity and high rates of multidrug resistance of conventional chemotherapy. Immunotherapy offered a potential solution to these challenges; however, monoclonal antibody treatments have failed to meet preclinical expectations due to high rates of therapeutic resistance and immunogenic reactions. Single-chain variable fragment (scFv) antibodies linked to nanoparticles (NPs) represent an emerging approach that may address these limitations by improving tumor targeting, reducing immunogenicity, and enhancing drug delivery. This review examines the design, limitations, and therapeutic applications of scFv-functionalized NPs in the treatment of advanced solid tumors. Systematic searches across PubMed, GoogleScholar, and ClinicalTrials.gov databases were conducted with inclusion of 62 articles from 2010 to 2025. Future directions include engineering nanocarriers with dual sensitivities to the tumor microenvironment, targeting cancer stem cells to prevent relapse, and incorporating biomarker-driven patient selection to facilitate successful clinical translation.