One-step green synthesis of collagen nanoparticles using Ulva fasciata, network pharmacology and functional enrichment analysis in hepatocellular carcinoma treatment

Collagen nanoparticles (collagen-NPs) possess numerous applications owing to their minimal immunogenicity, non-toxic nature, excellent biodegradability and biocompatibility. This study presents a novel sustainable technique for one-step green synthesis of hydrolyzed fish collagen-NPs (HFC-NPs) using a hot-water extract of Ulva fasciata biomass. HFC-NPs were characterized using TEM, FTIR, XRD, ζ-potential analyses, etc. TEM revealed hollow spherical nanoparticles exhibiting an average diameter of 27.25 nm. Face-centered central composite design was employed to maximize the HFC-NPs yield. The highest HFC-NPs yield was 13.05 mg/mL, which was achieved when the initial pH level was 7, incubation period was 72 h, and HFC concentration was 15 mg/mL. Thereafter, the possibility of using HFC-NPs as a biosafe drug carrier for doxorubicin (DOX) was tested in-vitro. Interestingly, both HFC-NPs and DOX-loaded HFC-NPs showed anticancer activity against hepatocellular carcinoma 'HCC'. In silico protein-protein interaction (PPI), network pharmacology, and functional pathway enrichment analysis of the common predicted HFC and HCC core targets suggested the involvement of PI3K-Akt, JAK-STAT, TNF, and/or Toll-like receptor signaling pathways in the HFC anti-HCC effect. In conclusion, our in vitro and in silico analysis demonstrated the HFC-NPs therapeutic efficacy in HCC, reflecting their promising potential in the development of novel anticancer drugs for HCC treatment.