Engineering melanin nanoconjugates from rational synthesis to clinical translations

Melanin, a natural biopolymer, has become a very promising material for the development of multifunctional nanoconjugate due to its unique physicochemical properties, such as broadband UV-NIR absorption, redox activity, metal-chelating capacity, adhesive surface chemistry, and biocompatibility. Recent advances in nanotechnology have enabled the rational design of melanin-based nanoconjugates with enhanced structural control, multifunctionality, and biomedical performance. In this study, a comprehensive and critical overview of natural, synthetic and bioengineered melanin systems, with interest in melanin nanoconjugates that are achieved by integration with metal, polymer and carbon-based nanomaterials are presented. This type of synergistic combination of melanin enables the development of advanced hybrid platforms for drug delivery, photothermal and photodynamic therapy, bioimaging, biosensing, tissue engineering, and antioxidant therapy. Furthermore, this review critically examines current challenges associated with reproducibility, structural heterogeneity, large scale manufacturing, and in vivo safety, which is crucial for clinical applications. These limitations can be overcome through emerging strategies involving new synthesis procedures, advanced surface functionalization, bioengineering, and standardized manufacturing approaches, as discussed as potential solutions. Overall, melanin-based nanoconjugates represent a versatile and sustainable solution for next-generation therapeutics.