Human Cancer Cell Membrane-Coated Biomimetic Nanoparticles Reduce Fibroblast-Mediated Invasion and Metastasis and Induce T-Cells

Abstract

Biomimetic nanoparticles (NPs) combine the flexibility and reproducibility of synthetic materials with the functionality of biological materials. Here, we developed and characterized biomimetic poly­(lactic-co-glycolic acid) (PLGA) NPs coated with human cancer cell membrane fractions (CCMFs) to form CCMF-coated PLGA (CCMF-PLGA) NPs. We evaluated the ability of these CCMF-PLGA NPs to disrupt cancer cell–stromal cell interactions and to induce an immune response. Western blot analysis verified the plasma membrane purity of CCMFs. Confocal fluorescence microscopy and flow cytometry confirmed the presence of intact membrane-associated proteins including CXCR4 and CD44 following membrane derivation and coating. CCMFs and CCMF-PLGA NPs were capable of inhibiting cancer cell migration toward human mammary fibroblasts. Intravenous injection of CCMF-PLGA NPs significantly reduced experimental metastasis in vivo. Following immunization of Balb/c mice, near-infrared fluorescence imaging confirmed the migration of NPs to proximal draining lymph nodes (LNs). A higher percentage of CD8+ and CD4+ cytotoxic T-lymphocyte populations was observed in spleens and LNs of CCMF-PLGA NP-immunized mice. Splenocytes isolated from CCMF-PLGA NP-immunized mice had the highest number of interferon gamma-producing T-cells as detected by the ELISpot assay. CCMF-PLGA NPs hold promise for disrupting cancer cell–stromal cell interactions and for priming the immune system in cancer immunotherapy.

Comparison of the effect of rhodium citrate-associated iron oxide nanoparticles on metastatic and non-metastatic breast cancer cells

“…One of the major problems in cancer control is the metastatic ability of the cells. Therefore, the synthesis of drugs and nanomedicines that control this process should be stimulated (Jin et al 2019). Although the involved mechanism is not yet understood, the reduction in migration of MDA-MB-231 cells treated with ruthenium-based metal complexes has been reported (Cao et al 2015).…”

Biomimetic Nanoparticles Camouflaged in Cancer Cell Membranes and Their Applications in Cancer Theranostics

“…Based on the density difference between the plasma membrane and other cellular factions, differential centrifugation is mainly used for plasma membrane isolation. However, we found that gradient centrifugation was superior to differential centrifugation in terms of purity of isolated cell membrane fractions (19). Commonly used gradients include discontinuous sucrose, and self-generated Percoll or iodixanol gradients (48,49).…”

“…The RBC membrane was found to act as a nanosponge for toxins, and bestowed a longer circulation pharmacokinetic profile than uncoated NPs (3). Since this initial study, cell membrane coating technology has significantly expanded to the use of membranes from platelets (4)(5)(6)(7)(8) and from nucleated cells, such as macrophages (9)(10)(11)(12), neutrophils (13), beta cells (14), and cancer cells (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). The use of cancer cell plasma membranes has attracted attention because these membranes carry tumor-specific receptors and antigens that play a role in cancer cell proliferation, invasion, and metastasis.…”

Cancer Cell Membrane-Coated Nanoparticles for Cancer Management

“…It also successfully traveled to draining lymph nodes post-transdermal injection and facilitated potent tumor-specific immune responses [64]. In another unique nanovaccine design, melanoma cell membrane fractions were coated onto PLGA NPs and their ability to effect fibroblast-mediated invasion, change experimental metastasis, and induce an immune response in immunocompetent mice was evaluated [43]. The nanovaccine successfully inhibited cancer cell migration toward fibroblasts, significantly decreased metastatic burden, and increased cytotoxic T lymphocytes, indicating membrane-wrapped nanovaccines not only show potential as antigen delivery vehicles for primary tumor elimination, but also as metastasis inhibitors.…”

“…Cancer cells are robust and easy to culture in large volumes in vitro for mass membrane collection and also possess the unique ability to self-target homologous cells (also known as homotypic targeting), unlike most other membrane donors [8,9,40,42]. This unique ability translates to cancer cell membrane-wrapped NPs (CCNPs), which retain the ability to homotypically target primary tumors and metastatic nodules [40,[42][43][44][45] ( Figure 2). Additionally, CCNPs display unprecedented binding and selective uptake in tumor cells matched to those from which they were derived, as well as have reduced immune clearance after systemic administration compared to non-coated NPs [22,40,42,44,46,47].…”