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Self-assembled Lipid Nanoparticles for Killing Triple Negative Breast Cancer Cells
Wahida Rahaman1, Arabinda Chaudhuri1
1Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal, 741246, India.
Abstract:
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.
Insights
New pegylated lipopeptides form self-assembled lipid nanoparticles (LNPs) that effectively kill triple negative breast cancer (TNBC) cells. These LNPs show targeted delivery and significant cancer cell death with minimal impact on healthy cells.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Triple negative breast cancer (TNBC) is aggressive and hard to treat due to lack of ER, PR, and HER2.
- Current treatments for TNBC have limitations, necessitating novel therapeutic strategies.
Purpose of the Study:
- To develop and characterize self-assembled lipid nanoparticles (LNPs) from novel pegylated lipopeptides for targeting and killing TNBC cells.
- To evaluate the cellular uptake and efficacy of these LNPs in TNBC models.
Main Methods:
- Synthesis of pegylated lipopeptides with n-hexadecyl tails and RGDK/CGKRK targeting peptides.
- Formation and characterization of self-assembled LNPs using SEM.
- Assessment of cellular uptake in various cell lines (MCF-7, MDA-MB-231, HEK-293, HFF).
- Evaluation of TNBC cell killing efficacy using a JAK2 inhibitor (WP 1066) loaded LNPs.
Main Results:
- Self-assembled spherical LNPs were successfully formed.
- Pegylated CGKRK-lipopeptide LNPs showed significantly higher cellular uptake than pegylated RGDK-lipopeptide LNPs.
- WP 1066 loaded pegylated RGDK-lipopeptide LNPs killed approximately 60% of TNBC cells while only affecting 20% of non-cancerous HEK-293 cells.
Conclusions:
- Self-assembled pegylated lipopeptide LNPs are promising for TNBC therapy.
- These LNPs demonstrate targeted delivery and potent anti-cancer activity.
- The findings support further preclinical investigation in animal models for TNBC.
