Fabrication and Functional Modification Strategies of Squid Ink-Derived Nanoparticles: From Natural Melanin to Multifunctional Biomaterials

Squid ink has recently garnered considerable attention as a natural melanin source for the development of biocompatible nanomaterials. Although numerous studies have explored the biological and therapeutic applications of squid ink, the fabrication and modification strategies for squid ink-derived nanoparticles (SINPs) have yet to be comprehensively reviewed. This paper provides an integrated overview of current extraction, purification, and functionalization strategies for SINPs, with a particular focus on how functionalization approaches modulate their physicochemical characteristics and biological behaviors. The review begins by outlining the natural mechanisms of melanin formation and summarizing common extraction methods-including centrifugation, ultrasonication, and dialysis. Subsequently, various surface modification and hybridization techniques-including polymer coating, incorporation of metallic elements (e.g., Se and Fe), and loading of photosensitizers-are compared in terms of their contributions to functional enhancement. Finally, the challenges of reproducibility, batch-to-batch variability, and scalable manufacturing are discussed, outlining future directions for the development of squid ink-derived nanomaterials into standardized biomedical platforms.