Cell-mediated and cell membrane-coated nanoparticles for drug delivery and cancer therapy

Abstract

Nanotechnology-based drug delivery platforms have been developed over the last two decades because of their favorable features in terms of improved drug bioavailability and stability. Despite recent advancement in nanotechnology platforms, this approach still falls short to meet the complexity of biological systems and diseases, such as avoiding systemic side effects, manipulating biological interactions and overcoming drug resistance, which hinders the therapeutic outcomes of the NP-based drug delivery systems. To address these issues, various strategies have been developed including the use of engineered cells and/or cell membrane-coated nanocarriers. Cell membrane receptor profiles and characteristics are vital in performing therapeutic functions, targeting, and homing of either engineered cells or cell membrane-coated nanocarriers to the sites of interest. In this context, we comprehensively discuss various cell- and cell membrane-based drug delivery approaches towards cancer therapy, the therapeutic potential of these strategies, and the limitations associated with engineered cells as drug carriers and cell membrane-associated drug nanocarriers. Finally, we review various cell types and cell membrane receptors for their potential in targeting, immunomodulation and overcoming drug resistance in cancer.

Keywords: Cell membrane-based drug delivery; cancer drug resistance; cell-mediated drug delivery; drug carriers; membrane receptors; nanoparticles.

Figure 1

Preparation of cell/cell membrane-based payload delivery and its applications. CRISPR: clustered regularly interspaced short palindromic repeats; Cas9: CRISPR associated protein 9; IPTG: isopropyl β-D-1-thiogalactopyranoside

Figure 2

Illustration showing major cell types and the use of cell membranes in drug delivery, immunotherapy, and immunomodulation. CAR: chimeric antigenic receptor

Figure 3

Current and potential cell types used for design of nanoparticle-based drug delivery in cancer therapy and immunomodulation along with their strategies to improve drug delivery (strategies include nanoparticle hitchhiking, autocrine signaling via cell membrane-bound nanoparticles, cell surface engineering and cell membrane-coated nanoparticle-based drug delivery). BBB: blood brain barrier

Figure 4

Potential cell surface proteins and their complements to be used in immunomodulation, immunotherapy, and targeted-drug delivery applications. t-SNARE/v-SNARE: target snap receptor/vesicle snap receptor; PS: phosphatidylserine; C1q: complement component 1q; SCARF-1: scavenger receptor class-F, member-1; Gp1b: glycoprotein-Ib; TSP-2: thrombospondin-2; SIRPα: signal regulatory protein α; CD: cluster of differentiation; ICAM: intercellular adhesion molecule; LFA-1: lymphocyte function-associated antigen-1; MAC-1: macrophage adhesion ligand-1; VLA: very late antigen; PAMP: pathogen associated molecular pattern; DAMP: damage-associated molecular pattern; PD-1/PD-2: programmed cell death protein-1/programmed cell death protein-2; PD-L1/PD-L2: programmed death-ligand-1/programmed death-ligand-2; CTLA-4: cytotoxic t-lymphocyte-associated protein-4; TRAIL: tumor necrosis factor-related apoptosis-inducing ligand; TNF: tumor necrosis factor; B7-H6: B7 homolog 6; MIC: MHC class I polypeptide-related sequence; H60: histocompatibility protein-60; NKp: natural cytotoxicity triggering receptor; NKG: natural killer cell granule protein; KIR: killer-cell immunoglobulin-like receptor; LIR: leukocyte immunoglobulin-like receptor; HMGβ1: high-mobility group protein β1; RAGE: receptor for advanced glycation end products