Targeting Specificity of Liposomes Coated with Isolated Membranes from Cancer and Macrophage Cell Lines

Abstract

Chemotherapy is currently one of the mainstream treatments for cancers and is often unsuccessful in the treatment role due to a lack of target specificity. This lack of specificity leads to an abundance of off‐target effects and inadequate therapeutic concentrations due to the harsh side effects of the chemotherapeutics which commonly include alopecia, fatigue, and a compromised immune system. More specific drug delivery mechanisms are needed to address these issues and increase chemotherapeutic efficacy. One promising method was recently developed when investigators successfully synthesized and tested a macrophage membrane encapsulated liposome (MEL) in murine models. The chemotherapeutic loaded MEL demonstrated increased targeting, biomimetic capability, and was more effective at eliminating metastatic lung lesions of 4T1 murine breast cancer when compared to chemotherapeutic loaded liposomes and free chemotherapeutics alone. Based on that information, this study proposed that THP‐1 human macrophage membrane could be used to synthesize human compatible MELs and successfully target MDA MB 231 human breast adenocarcinoma cells while demonstrating decreased uptake in THP‐1 cells. Human MELs were successfully synthesized as confirmed by SDS‐PAGE, but preliminary uptake studies of fluorescent cargo disproved the initial hypothesis as MEL uptake was significantly increased in THP‐1 cells and statistically static in MDA MB 231 cells compared to control liposomes. However, these findings presented a new interest in investigating MDA MB 231 membrane encapsulated liposomes and uptake testing is currently ongoing. Investigation into membrane encapsulated liposome stability and cytotoxicity in MDA MB 231 and THP‐1 cultures will be performed, as well as testing to compare macrophage activation in the presence of the encapsulated liposome variants. This work will beneficial in understanding the specificity to MDA MB 231 and THP‐1 cells conferred by various cell membranes and can ultimately aid in the development of more specific drug delivery systems to improve the efficacy of chemotherapy while decreasing off‐target effects.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.