Original ArticleThe ligand (s) anchored lipobrid nanoconstruct mediated delivery of methotrexate: an effective approach in breast cancer therapeutics

The present study was designed to engineer surface-anchored and methotrexate loaded lipobrid nano-constructs for targeting breast cancer. Ligands (fucose, galactose and mannose) anchored lipobrid nano-constructs were used to compare and assess delivery efficiency in breast cancer cell lines as well as in DMBA induced breast cancer animal model. The developed and characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, bio-distribution, changes in tumor volume and animal survival. Our results show greater cellular uptake, cytotoxicity at low IC50, apoptosis with altered lysosomal membrane permeability and greater rate of degradation of lysosomal membrane. We saw better bioavailability and tumor targeting efficiency with minimum secondary organ drug distribution. The significant reduction was seen in tumor burden with ligand anchored lipobrids in comparison to plain and MTX-lipobrid formulations. In conclusion, fucose anchored MTX-lipobrid formulation showed promising results, and warrants to explore the development of therapeutic interventions for breast cancer.

Graphical AbstractThe graphical abstract illustrates the following: (A) formulation development of methotrexate loaded lipobrids, (B) activation of three different ligands (fucose, mannose and galactose) at acidic pH, (C) surface modification of lipobrids with the ligands for targeted delivery in cancer therapy. Final step (D) shows ligand-receptor mediated endocytosis followed by the degradation of lipobrid. It releases the entrapped methotrexate in the cytoplasm, and eventually the drug enters the nucleus leading to the cell cycle arrest by the inhibition of DNA synthesis.230