Abstract 266: Differential collective cell migratory behaviors modulated by phospholipid nanoparticles

Abstract Phospholipid nanoparticles have been actively explored for biological and biomedical applications. These nanoparticles display excellent cargo encapsulation efficiency, high water dispersibility, and outstanding biocompatibility, rendering them highly attractive for cancer nanomedicine applications. While the promising utilizations of phospholipid nanoparticles for cancer theranostic have been widely documented, the cellular biophysical responses elicited by phospholipid nanoparticles have been less investigated. Notably, the effects of phospholipid nanoparticles on collective cancer cell behaviors have not been well delineated. In fact, most of the studies examining nanoparticle-cancer interactions have focused largely on the nanoparticle toxicity on individual cells, but paid little attention to other nanoparticle effects on multicellular systems and their collective behaviors. A better appreciation of the effects of nanoparticles on multicellular system dynamics is necessary as collective cancer cell behaviors are central to the regulation of various processes, particularly cancer invasion and metastasis. Motivated by this, we sought to interrogate the effects of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) nanoparticles, which are some of the most commonly used phospholipid nanoparticles for cancer nanomedicine, on the collective behaviors of healthy and cancerous breast epithelial cell monolayers. DSPE-PEG nanoparticles with two sizes (i.e., 20 and 60 nm) and three surface functional groups (i.e., COOH, OCH3, and NH2) as well as three types of breast epithelial cell sheets with varying malignancy potential (i.e., MCF-10A, MCF-7, and MDA-MB-231) were used in this work. Utilizing a series of microscopy and molecular biology techniques and quantitative image analysis, we comprehensively examined the collective cell migratory dynamics in the absence and presence of DSPE-PEG nanoparticles. We noted that DSPE-PEG nanoparticles retarded the migration of the healthy MCF-10A epithelial cell sheets. In contrast, the cancerous MCF-7 and MDA-MB-231 cell sheets experienced accelerated collective migration in the presence of the nanoparticles. Moreover, these nanoparticles altered the migration directionality of the cancerous breast cell sheets. We ascribed the differential nanoparticle-modulated collective cell migratory behaviors to changes in the stiffness of the cell nuclei, cytoplasm, and cell-cell junctions, as well as the reorganization of the cellular actin filament networks after the nanoparticle-cell interactions. We anticipate that this study will provide a deeper insight into the nanomaterial-cancer interactions and aid the formulation of phospholipid nanoparticles for more effective and safer cancer theranostic and nanomedicine applications. Citation Format: Kenry, Bin Liu. Differential collective cell migratory behaviors modulated by phospholipid nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 266.