Membrane engineering of cell membrane biomimetic nanoparticles for nanoscale therapeutics

Abstract

In recent years, cell membrane camouflaging technology has emerged as an important strategy of nanomedicine, and the modification on the membranes is also a promising approach to enhance the properties of the nanoparticles, such as cancer targeting, immune evasion, and phototherapy sensitivity. Indeed, diversified approaches have been exploited to re-engineer the membranes of nanoparticles in several studies. In this review, first we discuss direct modification strategy of cell membrane camouflaged nanoparticles (CM-NP) via noncovalent, covalent, and enzyme-involved methods. Second, we explore how the membranes of CM-NPs can be re-engineered at the cellular level using strategies such as genetic engineering and membranes fusion. Due to the innate biological properties and excellent biocompatibility, the functionalized cell membrane-camouflaged nanoparticles have been widely applied in the fields of drug delivery, imaging, detoxification, detection, and photoactivatable therapy.

Keywords: cell membrane camouflaged nanoparticles; membrane engineering; nanoscale therapeutics.

FIGURE 1

Preparation and modification of cytomembranes camouflaged nanoparticles. (A) The functional targeting ligands were directly modified on the membrane surface of CM‐NPs after the CM‐NPs had been successfully prepared. (b) The living cell membranes were modified before extraction

FIGURE 2

Strategies for CM‐NP modification. (A) Functional lipids can be spontaneously integrated into the phospholipid bilayers by hydrophobic interactions. (B) Several molecules can interact with membrane proteins, such as antigens and certain peptides bind to the receptors on the cytomembranes relying on the ionic bond and hydrophobic interactions. (C) In the avidin‐biotin reaction, biotins firstly anchor to the amino groups on cell membranes to construct the biotinylated CM‐NP. Then, the biotinylated groups conjugate with avidin/streptavidin anchored to the therapeutic molecules. (D) The therapeutic molecules conjugated to maleimide groups can link to the membranes via thiol groups. (E) N3 decorated on the membrane conjugates to the DBCO compound linked with therapeutic molecules by the copper‐free click chemical reaction. (F) Engineered cells express the desired products on the surface by transcription and translation of the gene. (G) Two different kinds of cytomembranes can be fused and the cytomembrane of hybrid cells can co‐expressed functional proteins derived from different cells

FIGURE 3

The tumor‐associated gene was integrated into the genome via transduction of retrovirus, and expressed CAR on membrane. The CAR‐T CM‐NPs targeted the TAAs expressed on cancer cells and released photothermal nanoparticles to eliminate tumor cells. Recreated from Ma et al. ⁵⁰

FIGURE 4

Membrane materials were respectively extracted from cancer cells and RBCs and then fused together. The hybrid membranes retained the membrane components derived from two different cells and played the inherent functions of two different kinds of cells

FIGURE 5

The leukocyte membrane was pre‐engineered with azide (N3) via intrinsic biosynthesis and metabolic incorporation of phospholipids. Dibenzocyclooctyne (DBCO)‐modified T‐cell stimuli (such as anti‐CD28 and pMHC‐I) could be decorated through copper‐free click chemistry. The biomimetic aAPCs efficiently expanded and stimulated naïve CD8+ T cells ex vivo. Recreated from Zhang et al. ⁴⁴

FIGURE 6

Cyanine dye DiR was inserted into bilayer lipid membrane by noncovalent interactions, and modified CM‐NPs were absorbed by tumor cells. Under near‐infrared laser, DiR incorporated into CM‐NPs showed increased fluorescence. Owing to the accumulation of DiR in cancer cells, in vivo imaging and biodistribution of tumors could be realized. Recreated from Su et al. ⁹⁷