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

**Authors:** Jung Min Shin

PMC · DOI: 10.3390/md24030089 · Marine Drugs · 2026-02-24

## TL;DR

This paper reviews methods to create and modify squid ink nanoparticles, highlighting their potential as biocompatible materials for biomedical applications.

## Contribution

The paper offers a comprehensive review of fabrication and functionalization strategies for squid ink-derived nanoparticles, emphasizing their physicochemical and biological modulation.

## Key findings

- Common extraction methods for squid ink nanoparticles include centrifugation, ultrasonication, and dialysis.
- Surface modification techniques like polymer coating and metallic element incorporation enhance nanoparticle functionality.
- Challenges such as reproducibility and scalability need addressing for biomedical standardization.

## Abstract

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.

## Linked entities

- **Chemicals:** Se (PubChem CID 5460640), Fe (PubChem CID 23925)

## Full-text entities

- **Genes:** SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, DCT (dopachrome tautomerase) [NCBI Gene 1638] {aka OCA8, TRP-2, TYRP2}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, FZD2 (frizzled class receptor 2) [NCBI Gene 2535] {aka Fz2, OMOD2, fz-2, fzE2, hFz2}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, MRC1 (mannose receptor C-type 1) [NCBI Gene 4360] {aka CD206, CLEC13D, CLEC13DL, MMR, MRC1L1, bA541I19.1}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, TYR (tyrosinase) [NCBI Gene 7299] {aka ATN, CMM8, OCA1, OCA1A, OCAIA, SHEP3}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}
- **Diseases:** vitiligo (MESH:D014820), ARS (MESH:D054508), CRWI (MESH:D011832), cancer (MESH:D009369), hypoxia (MESH:D000860), disc degeneration (MESH:D055959), hypoxic (MESH:D002534), inflammation (MESH:D007249), skin depigmentation (MESH:D012871), solid (MESH:D018250), epidermal hyperplasia (MESH:D006965), Infected (MESH:D007239), injury to (MESH:D014947), hyperpigmentation (MESH:D017495), bacterial infections (MESH:D001424), cytotoxicity (MESH:D064420), neurodegeneration (MESH:D019636)
- **Chemicals:** DCFH-DA (MESH:C029569), PDA (MESH:C568283), indoles (MESH:D007211), NaN3 (MESH:D019810), ROS (MESH:D017382), sodium (MESH:D012964), borax (MESH:C018851), tacrolimus (MESH:D016559), magnesium (MESH:D008274), Se NPs (MESH:C059702), PEG (MESH:D011092), amino acid (MESH:D000596), RhB (MESH:C029773), H&amp;E (MESH:D006371), H2O2 (MESH:D006861), mucopolysaccharides (MESH:D006025), methanol (MESH:D000432), ascorbic acid (MESH:D001205), ginsenoside Rc (MESH:C044462), polyphenols (MESH:D059808), catechol (MESH:C034221), amine (MESH:D000588), acrylic acid (MESH:C036658), Metal (MESH:D008670), DPPH (MESH:C004931), graphene (MESH:D006108), sulfur (MESH:D013455), dopaquinone (MESH:C035157), HCl (MESH:D006851), SA (MESH:D000464), Melanin (MESH:D008543), o-quinone (MESH:C025225), PTIO (MESH:C079391), Se (MESH:D012643), Cu (MESH:D003300), l-tyrosine (MESH:D014443), indole (MESH:C030374), mannose (MESH:D008358), nitrogen (MESH:D009584), saline (MESH:D012965), pheomelanin (MESH:C018362), l-DOPA (MESH:D007980), dopamine (MESH:D004298), MTT (MESH:C070243), water (MESH:D014867), PS (MESH:D010758), polymer (MESH:D011108), quinone (MESH:C004532), 3AGM (-), gallium (MESH:D005708), DPG (MESH:C027773), hydrogen (MESH:D006859), calcium (MESH:D002118), MXene (MESH:C000723374), dopachrome (MESH:C001123), eumelanin (MESH:C041877), acrylamide (MESH:D020106), catecholamine (MESH:D002395), PVA (MESH:D011142), oxygen (MESH:D010100)
- **Species:** Escherichia coli (E. coli, species) [taxon 562], Sepia officinalis (common cuttlefish, species) [taxon 6610], PX clade (clade) [taxon 569578], Mus musculus (house mouse, species) [taxon 10090], Sepiidae (cuttlefishes, family) [taxon 6608], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** U-87 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0022), SINP-2D — Mus musculus (Mouse), Hybridoma (CVCL_U038), SaOs-2 — Homo sapiens (Human), Osteosarcoma, Cancer cell line (CVCL_0548)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13028319/full.md

## References

89 references — full list in the complete paper: https://tomesphere.com/paper/PMC13028319/full.md

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Source: https://tomesphere.com/paper/PMC13028319