Vitamin C Conjugates in Biomedicine: A Comprehensive Exploration with Drugs, Polymers, Proteins, and Peptides

Vitamin-drug conjugates are formed by linking a drug to a vitamin, either directly or through a spacer, to facilitate recognition and binding to receptors overexpressed on bacterial, cancer, or targeted cells. This strategy, often described as a "Trojan horse" approach, enhances intracellular drug accumulation and helps overcome resistance. Drugs conjugated with essential nutrients, such as vitamins, are actively taken up by cells for survival, thereby increasing therapeutic efficacy. Vitamin C-drug conjugates, including derivatives of diclofenac, aspirin, and naproxen, have demonstrated improved transport across the blood-brain barrier via SVCT-mediated uptake, offering potential for the treatment of neurodegenerative disorders. Similarly, conjugation with antivirals such as saquinavir improves oral absorption and systemic bioavailability by bypassing efflux mechanisms. Beyond small-molecule drugs, vitamin conjugates with polymers, lipids, peptides, natural compounds, and proteins have emerged as innovative strategies for targeted delivery. The incorporation of vitamin C into nanostructures, such as gold nanoparticles, enhances oxidative stability and promotes intracellular delivery through endocytosis. Protein conjugates, utilizing carriers such as HSA, BSA, and β-lactoglobulin, facilitate systemic transport, while peptide conjugates leverage the antioxidant activity of vitamin C in conjunction with peptide-based targeting, providing synergistic benefits in cosmetics and dermatology. Collectively, these studies highlight vitamin C conjugation as a versatile platform for precision medicine and targeted therapy.