Polymeric biomaterial-inspired cell surface modulation for the development of novel anticancer therapeutics

Abstract

Immune cell-based therapies are a rapidly emerging class of new medicines that directly treat and prevent targeted cancer. However multiple biological barriers impede the activity of live immune cells, and therefore necessitate the use of surface-modified immune cells for cancer prevention. Synthetic and/or natural biomaterials represent the leading approach for immune cell surface modulation. Different types of biomaterials can be applied to cell surface membranes through hydrophobic insertion, layer-by-layer attachment, and covalent conjugations to acquire surface modification in mammalian cells. These biomaterials generate reciprocity to enable cell–cell interactions. In this review, we highlight the different biomaterials (lipidic and polymeric)-based advanced applications for cell–surface modulation, a few cell recognition moieties, and how their interplay in cell–cell interaction. We discuss the cancer-killing efficacy of NK cells, followed by their surface engineering for cancer treatment. Ultimately, this review connects biomaterials and biologically active NK cells that play key roles in cancer immunotherapy applications. Graphical Abstract

Biomaterial-Mediated Exogenous Facile Coating of Natural Killer Cells for Enhancing Anticancer Efficacy toward Hepatocellular Carcinoma

“…Specifically, the NK cell lytic-immunological synapse is activated by a series of sequential events: (1) interaction of NK-to-target cell interfaces, (2) secretion of cytotoxic granules and cytokines, and (3) target cell lysis . In the structure of DSPE PEG -diPEG-LBA, DSPE lipid tail is anchored into the NK cell membrane through hydrophobic interactions , for sufficient surface presentation of LBA molecules on NK cells. Subsequently, the head LBA moiety is extracellularly exposed for ASGPR targeting.…”

“…Natural killer (NK) cells exhibit potential tumor-killing efficacy against various tumor cells without cytokine syndrome through two major functions: (1) cell–cell interaction-dependent cytotoxicity and (2) secretion of cytokines for immune modulation. These functions are necessary for adaptive immune responses through NK cell activation during host defense against solid tumors. – NK cells express their own cellular surface ligands, and they can easily recognize target cancer cells through encoded surface ligands and receptors, such as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Fas ligand (FasL), and NK group 2 member D (NKG2D). , Subsequent secretion of lytic granules (i.e., perforin and granzyme) can damage and kill cancer cells, and additionally released cytokines (i.e., TNF-alpha and IFN-gamma) also activate and orchestrate adaptive immunity as well …”

Optimized Design of Hyaluronic Acid–Lipid Conjugate Biomaterial for Augmenting CD44 Recognition of Surface-Engineered NK Cells

“…Alternatively, lipid anchor-mediated ex vivo NK cell engineering has emerged as a potential solution . This approach can effectively present various receptor/ligand components onto NK surfaces via hydrophobic interaction between the lipid anchor moiety in surface-immobilizable components and lipid bilayers of NK cell membranes without needing any genetic modification of NK cells. − In contrast to other conventional single-cell surface modulations such as chemical conjugation by forming covalent bonds and serial layer-by-layer coating, lipid anchor-mediated immobilization of surface components can uniformly modify cell surfaces and preserve the intrinsic properties of cells without toxicity issues. , …”

Ex Vivo Surface Decoration of Phenylboronic Acid onto Natural Killer Cells for Sialic Acid-Mediated Versatile Cancer Cell Targeting

“…Material-driven surface engineering of NK cells involves a variety of approaches, including direct chemical conjugation at the biorthogonal site, layer-by-layer deposition, or membrane insertion via hydrophobic interactions. , However, chemical conjugation and layer-by-layer strategies have certain limitations, thereby prone to disturb cell surface functionalities by interfering with cell division and cytotoxicity . Moreover, the hydrophobic insertion of lipidic materials on the cell surface offers an advantage over conventional methods .…”