Latest Advances in Biomimetic Cell Membrane-Coated and Membrane-Derived Nanovectors for Biomedical Applications

Abstract

In the last decades, many nanovectors were developed for different diagnostic or therapeutic purposes. However, most nanosystems have been designed using a "bottom-up" approach, in which the basic components of the nanovector become assembled to achieve complex and specific behaviors. Despite the fine control of formulative conditions, the complexity of these systems often results cumbersome and difficult to scale-up. Recently, biomimetic materials emerged as a complementary or alternative design approach through a "top-down strategy", using cell-derived materials as building blocks to formulate innovative nanovectors. The use of cell membranes as nanoparticle coatings endows nanomaterials with the biological identity and some of the functions of the cells they are derived from. In this review, we discuss some of the latest examples of membrane coated and membrane-derived biomimetic nanomaterials and underline the common general functions offered by the biomaterials used. From these examples, we suggest a systematic classification of these biomimetic materials based on their biological sources and formulation techniques, with their respective advantages and disadvantages, and summarize the current technologies used for membranes isolation and integration on nanovectors. We also discuss some current technical limitations and hint to future direction of the improvement for biomimetics.

Keywords: biomimetic; coating; drug delivery systems; membrane; nanomedicine; nanoparticle.

Figure 1

Schematic representation of how biomimetic nanovectors fit at the crossroads of biological therapies and synthetic nanovectors. For each field, its relative advantages are presented in green and disadvantages in red. This image was created using Biorender.com (accessed on 1 March 2022).

Figure 2

Schematic representation of the current biomimetic approach toolbox in term of source cells, biomimetic strategies, membrane proteins functions, and cargoes. This image was created with Biorender.com (accessed on 1 March 2022). EVs: extracellular vesicles; LMW: low molecular weight; MSCs: mesenchymal stem cells; NPs: nanoparticles; PTs: platelets; RBCs: red blood cells.

Figure 3

Schematic representation of biological therapies classified based on their resemblance to actual cells. This figure was produced using Biorender.com (accessed on 1 March 2022).

Figure 4

(a) Schematic representation of Oil nanospheres (Oli-NS), composed of a small oil droplet stabilized by red blood cells (RBC) derived membrane as detoxifying agent for organophosphate (OP). (b) Representative transmission electron microscope image of the spherical core–shell structure of Oil nanospheres. Scale bar = 100 nm. In vivo efficacy of Oil nanospheres against organophosphates intoxication. Mice were first injected intraperitoneally with oil or PLGA nanoparticles at different doses They were then challenged 2 min later by a single subcutaneous injection of organophosphates at 0.7 mg/kg. (c) Intoxication signs of mice were scored at 10 min post-injection. (d) Acetylcholinesterase (AChE) activity of blood measured at 10 min post-POX injection. (e) Survival rates of mice over 24 h after POX injection. In all studies, n = 5 per group. (** p < 0.01, *** p < 0.001, and **** p < 0.0001). Figure adapted with permission from ACS Nano 2019, 13, 7209–7215 (https://pubs.acs.org/doi/10.1021/acsnano.9b02773). Copyright 2019 American Chemical Society (accessed on 1 March 2022).

Figure 5

(a) Schematic representation of platelet membrane enclosed L-arginine and magnetite nanoparticles (PAMN) structure and in vivo targeting moieties. As PT membrane-coated biomimetic nanovector, PAMNs recapitulate the natural features of the PT membranes that expose on their surface specific binding proteins, providing active targeting to damaged vessels and immune escape. Through the mimetic properties of PT membranes and the application of a magnetic field (MF), the PAMNs reach the stroke lesion more quickly to achieve rapid targeted delivery of L-arginine. The in situ generation of nitric oxide (NO) induces vasodilation and reduces PLT aggregation. (b) Scanning electron microscopy characterization showing the surface structure of PAMNs. (c) NIR images of mice before and after injection with labeled PAMNs over time and their relative quantification (d). (e) Ex vivo NIR imaging of excised major organs 6 h after PAMN injection and its relative quantification (**: p < 0.01) (f). (g) Color-coded images showing blood reperfusion in the ischemic lesion within 4 h after thrombus formation that is comparable to the recognized therapeutic time window (4.5 h). Scale bar: 1 mm and their relative quantification (h). Figure adapted with permission from ACS Nano 2020, 14, 2024–2035 (https://pubs.acs.org/doi/abs/10.1021/acsnano.9b08587). Copyright 2019 American Chemical Society (accessed on 1 March 2022).

Figure 6

(a) Schematic representation of cellular nanosponges inhibiting SARS-CoV-2 infectivity. The nanosponges are formulated by wrapping polymeric nanoparticles with cell membranes from target cells such as lung epithelial cells and macrophages (MΦs). The resulting nanosponges (denoted “Epithelial-NS” and “MΦ-NS”, respectively) inherit the surface antigens of the source cells and serve as decoys to bind with SARS-CoV-2. To block viral entry and inhibit viral infectivity. (b) Epithelial-NS, (c) MΦ-NPs, and (d) nanosponges made from red blood cell membranes (control) was tested using live SARS-CoV-2 viruses on Vero E6 cells. In all data sets, n = 3. Data are presented as mean + standard deviation. Horizontal dashed lines mark the zero levels. Figure adapted with permission from Nano Lett. 2020, 20, 5570–5574 (https://pubs.acs.org/doi/10.1021/acs.nanolett.0c02278). Copyright 2019 American Chemical Society (accessed on 1 March 2022).

Figure 7

(a) Schematic illustration of the use of cancer cells membrane fraction-coated PLGA nanoparticles (CCMF-PLGA-NPs) to inhibit fibroblasts-cancer cells interactions and induce antitumor immunity via antigen presenting cells. (b) Representative TEM images of U87 cells-derived CCMF-PLGA-NPs (U87-CXCR4 CCMF-PLGA NPs) with insets showing high-magnification images. Scale bar is 20 nm. (c) Representative fluorescence images of major organs harvested at 24 h post injection of DiR-labelled PLGA particles (PLGA-DiR), U87 membrane fractions (U87-CXCR4-MFs), or U87-CXCR4 CCMF-PLGA NPs (100 μg for each). H, heart; Li, liver; Sp, spleen; M, muscle; Lu, lung; K, kidney; I, intestine; and St, stomach. (d) Pharmacokinetic curves of PLGA NPs, U87-CXCR4 MFs, and U87-CXCR4 CCMF-PLGA NPs in mouse plasma over a period of 24 h post injection of NPs (100 μg for each) through the tail vein. (e) Ex vivo bioluminescence images of metastatic nodules in lung after injection of 231-luciferase labelled CCMF-PLGA (231-luc CCMF PLGA NPs). (f) Metastatic burden quantification in lungs determined from the percentage of metastatic nodule area to the total lung area. * p < 0.05 (n = 5). Figure adapted with permission from ACS Appl. Mater. Interfaces 2019, 11, 7850–7861 (https://pubs.acs.org/doi/10.1021/acsami.8b22309). Copyright 2019 American Chemical Society (accessed on 1 March 2022).

Figure 8

Schematic representation of the structure and functions of leukosomes. EPR: enhanced permeability and retention effect. Image adapted from [77] under creative commons authorization.