Preparation and biomedical applications of artificial cells

Abstract

Artificial cells have received much attention in recent years as cell mimics with typical biological functions that can be adapted for therapeutic and diagnostic applications, as well as having an unlimited supply. Although remarkable progress has been made to construct complex multifunctional artificial cells, there are still significant differences between artificial cells and natural cells. It is therefore important to understand the techniques and challenges for the fabrication of artificial cells and their applications for further technological advancement. The key concepts of top-down and bottom-up methods for preparing artificial cells are summarized, and the advantages and disadvantages of the bottom-up methods are compared and critically discussed in this review. Potential applications of artificial cells as drug carriers (microcapsules), as signaling regulators for coordinating cellular communication and as bioreactors for biomolecule fabrication, are further discussed. The challenges and future trends for the development of artificial cells simulating the real activities of natural cells are finally described.

Keywords: Artificial cells; Bioreactors; Bottom-up approach; Cellular communication; Microcapsules.

Graphical abstract

Fig. 1

The fabrication of artificial cells using top-down or bottom-up approaches.

Fig. 2

Common bottom-up methods for the fabrication of artificial cells. (a) Thin-film hydration strategy: (a1) gentle hydration method, (a2) electro-formation method. (b) Emulsion templating strategies: (b1) water/oil (W/O) emulsion transfer method, (b2) water/oil/water (W/O/W) double emulsion template method.

Fig. 3

The calcium absorption approaches for forming GUVs of uniform size. (a) Schematic diagram of the two approaches: (a₁) the ions adsorption layer method and (a₂) the mineral adsorption layer method. (b) Fluorescent GUVs synthesized by method (a₁). (c) The fluorescent GUVs layer prepared by method (a₂) [64].

Fig. 4

Schematic of the three different cellular bionic hybridisation modes [36].

Fig. 5

(a) Schematic diagram showing the potential application of artificial cells for enhancing bone formation via controlled release of ACP clusters and drugs upon external stimulation. PC: phosphatidylcholine. PS: phosphatidylserine. (b) The morphology of artificial cells, (c) the particle size distribution of artificial cells, (d) the analysis of cluster motion of artificial cells under the action of a magnetic field, (e) the statistical chart of time, displacement, and instantaneous rate of artificial cells under magnetic drive.

Fig. 6

Diagram showing the interaction between T cell and the antigen-presenting cell (APC) or artificial antigen-presenting cell (aAPC) [128].

Fig. 7

(a) Schematic representation showing that hydrogen peroxide (H₂O₂) was generated in artificial cells by the oxidation of glucose in the presence of glucose oxidase (GOx) [136]. (b) A chemical communication pathway between two liposome-based artificial cells (lipid vesicle and proteinosome) [137]. (c) Schematic diagram of signaling molecule (AMP) generated by sender group and spread to receiver group [143].

Fig. 8

(a) Schematic diagram of artificial cells containing two compartment lipid vesicles, equipped with IVTT mixture for protein synthesis [28]. (b) Artificial cells with labeled liposome membrane by Rhodamine (red) and synthesize sfGFP (green) in liposome [106]. (c) Schematic diagram of artificial cells using aptamer grafted polymer hydrogel (left). The fluorescence expression of artificial cells (right) [152].

Fig. 9

(a) Schematic illustration and reaction equations of GOX@HRP-catalyzed Amplex Red oxidation for the production of resorufin after initiation by glucose [29]. (b) Schematic diagram of artificial cells by GOx-containing zeolitic imidazolate frameworks-8 (GOx-ZIF-8) and induce living cell response [30]. (c) The diagram of glucose sensing in engineered HEK-293 cells under low and high extracellular glucose level [153]. (d) The preparation of artificial cells and the illustration of NO synthesis through cascade enzymatic reactions [154].