Self‐assembled Lipid Nanoparticles for Killing Triple Negative Breast Cancer Cells.

Rahaman, Wahida; Chaudhuri, Arabinda

Triple negative breast cancers (TNBCs) lacking estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) on their cell surfaces are highly aggressive, difficult‐to‐treat and often relapse. Herein, we report on the self‐assembled lipid nanoparticles (LNPs) of two new pegylated lipopeptides for killing TNBCs (MDA‐MB‐231). The pegylated lipopeptides were synthesized by conjugating an n‐hexadecyl hydrophobic tail to one end of a (PEG)27 unit the other distal end of which was covalently grafted with two previously reported tumor targeting RGDK‐ and CGKRK‐ peptides. The SEM images of the self‐assembled LNPs formed upon dissolution of the pegylated lipopeptides in aqueous medium revealed formation of spherical aggregates. The degree of cellular uptake for the self‐assembled LNPs formed by the pegylated CGKRK‐lipopeptide were found to be significantly higher than that for the self‐assembled LNPs formed by the pegylated RGDK‐lipopeptide in MCF‐7, MDA‐MB‐231, HEK‐293 and HFF cells. Notably, about 60 % TNBCs (MDA‐MB‐231 cells) were killed upon treatment with commercially available potent JAK2 inhibitor (WP 1066) loaded LNPs of the pegylated RGDK‐lipopeptide. Contrastingly, the same treatment killed only about 20 % non‐cancerous HEK‐293 cells. The self‐assembled pegylated LNPs described herein open the door for undertaking preclinical studies in animal models for TNBCs.

TRIPLE-negative breast cancer; ESTROGEN receptors; PROGESTERONE receptors; DRUG carriers; CELL membranes

Chemistry - An Asian Journal, 2025, Vol 20, Issue 1, p1

1861-4728

Academic Journal

10.1002/asia.202401049