Polymeric Micelle of a Gelatin-Oleylamine Conjugate: A Prominent Drug Delivery Carrier for Treating Triple Negative Breast Cancer Cells.

Protein-based polymeric micelles are proven as effective colloidal drug carriers due to a high drug loading efficiency, sustained release, biocompatibility, and ease of permeation into the cell. Gelatin-based polymeric micelles find applications in treating rare cancerous cells like triple negative breast cancer cells (TNBC), which do not overexpress receptors on its surface. In the present work, we have modified the hydrophilic nature of gelatin into amphiphilic by conjugating with oleylamine using genipin as a cross-linking agent. Owing to amphiphilicity, gelatin-oleylamine conjugate (GOC) self-assembles to form micelles in the aqueous medium. NMR, FTIR, and UV-vis characterizations were used to identify cross-linkage between gelatin and oleylamine, while the results of DLS, confocal, and TEM confirmed aggregation of GOC monomers into micelles. Fluorescence measurement has revealed that the critical micellar concentration of GOC was 0.04 ± 0.01 mg/mL. According to DLS measurements, hydrodynamic size, ζ potential, and polydispersity index of GOC micelles were 230.6 ± 0.4 d. nm, -23.4 ± 0.2 mV, and 0.175 ± 0.008, respectively, proving its colloidal stability in solution at pH 7.4. Catechin was taken as a model antioxidant drug, and drug encapsulation efficiency of GOC micelle was determined to be 62 ± 3%. The cytotoxicity, fluorescent cell imaging, and flow cytometry analyses revealed that TNBC-type cells (MDA-MB-231) internalized drug-bound GOC nanocarriers (CT-GOC) and were involved in cell cycle arrest through G2/M phase-inducing cellular apoptosis. Further, CT-GOC exhibited a higher cellular toxicity to MDA-MB-231 cancerous cells but not in normal cells (NIH-3T3). The overall outcomes of physicochemical and biological measurements suggest that the prepared GOC micelles might be a promising drug carrier for novel anticancer agents in TNBC chemotherapy.