Abstract 3640: Cancer cell membrane coated biomimetic nanoparticles as decoys for disrupting cancer cell-stromal cell interactions
Authors: Jin Jiefu , Barnett James , Wildes Flonne , Nimaggada Sridhar , Bhujwalla Zaver 
Published: August 2019

Introduction: Biomimetic nanoparticles (NPs) combining synthetic and biological materials have flexibility and functionality for disruptive strategies.1 Stromal cells such as cancer associated fibroblasts (CAFs) mediate many of the aggressive characteristics of cancer and play a crucial role in proliferation, invasiveness, metastasis, and angiogenesis of cancer.2 NPs coated with cancer cell membrane fractions (CCMFs) inherit the repertoire of surface proteins from cancer cells, making them potentially useful as decoys to disrupt cancer cell-stromal cell interactions. Here, we coated cancer cell membranes onto poly(lactic-co-glycolic acid) (PLGA) NPs to form CCMF-PLGA NPs, and characterized their protein profile, size, purity, cellular internalization, and integrity. We investigated, for the first time, the ability of these “artificial cancer cells” to disrupt fibroblast-mediated migration and lung metastasis.

Method: CCMFs were isolated upon cell homogenization, and sucrose density gradient centrifugation. PLGA NPs were prepared by nanoprecipitation. CCMFs and PLGA NPs were mixed and physically extruded through a porous membrane to obtain CCMF-PLGA NPs. The protein profile of CCMFs was analyzed by western blot with antibodies against cell fraction markers.. The experimental lung metastasis model was established by intravenously injecting MDA-MD-231 cells constitutively expressing luciferase (231-luc) through the tail vein of nude mice. The treated group was inoculated with the same number of 231-luc cells mixed with CCMFs-PLGA NPs and injected weekly with CCMF-PLGA NPs in the following weeks. Lung metastasis was monitored in vivo for three consecutive weeks by bioluminescence imaging (BLI). At the end of treatment, lungs were isolated and inflated. Metastatic nodules were imaged with BLI and examined by histology.

Results: Plasma membrane purity was confirmed from western blot analysis that showed the significant enrichment of Na+/K+-ATPase, negligible amount of GPR78 or GAPDH in CCMFs. Confocal fluorescence microscopy and flow cytometry confirmed a “right-side” out orientation of CCMF-PLGA NPs and the integrity of membrane-associated proteins after membrane isolation and PLGA coating. When CCMFs or CCMF-PLGA NPs were added to HMFs in the transwell assay, fewer cancer cells migrated towards HMFs, identifying the unique ability of CCMF-PLGA NPs to disrupt HMF-cancer cell interactions. In the lung metastasis study, mice treated with CCMF-PLGA NPs had significantly less incidence and metastatic burden confirmed by BLI and histology. CCMF-PLGA NPs hold promise as decoys to disrupt cancer cell-stromal cell interactions.

References: 1. Fang, R. et al. Small 2015; 2. Shiga, K. et al. Cancers 2015. Supported by NIH R21 CA198243, R35 CA209960, and a grant from the Emerson Collective.

Citation Format: Jiefu Jin, James Barnett, Flonne Wildes, Sridhar Nimaggada, Zaver Bhujwalla. Cancer cell membrane coated biomimetic nanoparticles as decoys for disrupting cancer cell-stromal cell interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3640.