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.

The field of cancer therapy is actively pursuing highly effective self-targeted drug delivery materials endowed with exceptional properties. Recently, hyaluronic acid (HA), a naturally occurring polysaccharide, has been recognized as a potential target ligand for CD44 receptors, which are frequently expressed on various solid tumor cells targeted in cancer therapy. HA carbon quantum dots (CQDs) exhibit several advantageous properties, including a high surface area-to-volume ratio, small particle size, biocompatibility, and low cytotoxicity, making them ideal for biomedical applications, such as CD44-targeted drug delivery in ferroptosis-based cancer therapy. In this study, we synthesized HA-CQDs to enhance CD44-mediated ligand–receptor interactions targeting triple-negative breast cancer (TNBC). CQDs facilitate the intracellular generation of reactive oxygen species (ROS), leading to glutathione depletion. These processes result in crucial actions such as the downregulation of glutathione peroxidase 4, downregulation of solute carrier family 7 member 11, and inhibition of cystine intake. The subsequent intracellular ROS, originating from lipid peroxidation, induces ferroptosis. Our HA-CQDs engage CD44 receptors, selectively targeting TNBCs and enhancing cancer recognition. This interaction potentially enhances the nanoplatform-based CD44 targeted therapeutic effects in inducing ferroptosis.

Colon cancer (CC) belongs to the three major malignancies with a high recurrence rate. Therefore, a novel drug delivery system that can prevent CC recurrence while minimizing side effects is needed. Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) has recently been spotlighted as a protein drug that can induce apoptosis of cancer cells specifically. However, its short in vivo half-life is still a challenge to overcome. Hence, in this study, a gel-like mPEGylated coacervate (mPEG-Coa) delivery platform was developed through electrostatic interaction of mPEG-poly(ethylene arginylaspartate diglyceride) (mPEG-PEAD) and heparin for effective protection of cargo TRAIL, subsequently preserving its bioactivity. mPEG-Coa could protect cargo TRAIL against protease. Sustained release was observed for a long-term (14 days). In addition, recurrence of HCT-116 cells was suppressed when cells were treated with TRAIL-loaded mPEG-Coa for 7 days through long-term continuous supply of active TRAIL, whereas re-proliferation occurred in the bolus TRAIL-treated group. Taken together, these results suggest that our gel-like mPEG-Coa could be utilized as a functional delivery platform to suppress CC recurrence by exogenously supplying TRAIL for a long time with a single administration.

Colon cancer is a significant health concern. The development of effective drug delivery systems is critical for improving treatment outcomes. In this study, we developed a drug delivery system for colon cancer treatment by embedding 6-mercaptopurine (6-MP), an anticancer drug, in a thiolated gelatin/polyethylene glycol diacrylate hydrogel (6MP-GPGel). The 6MP-GPGel continuously released 6-MP, the anticancer drug. The release rate of 6-MP was further accelerated in an acidic or glutathione environment that mimicked a tumor microenvironment. In addition, when pure 6-MP was used for treatment, cancer cells proliferated again from day 5, whereas a continuous supply of 6-MP from the 6MP-GPGel continuously suppressed the survival rate of cancer cells. In conclusion, our study demonstrates that embedding 6-MP in a hydrogel formulation can improve the efficacy of colon cancer treatment and may serve as a promising minimally invasive and localized drug delivery system for future development.

Current cytokine-based natural killer (NK) cell priming techniques have exhibited limitations such as the deactivation of biological signaling molecules and subsequent insufficient maturation of the cell population during mass cultivation processes. In this study, we developed an amphiphilic trigonal 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-polyethylene glycol (PEG) material to assemble NK cell clusters via multiple hydrophobic lipid insertions into cellular membranes. Our lipid conjugate-mediated ex vivo NK cell priming sufficiently augmented the structural modulation of clusters, facilitated diffusional signal exchanges, and finally activated NK cell population with the clusters. Without any inhibition in diffusional signal exchanges and intrinsic proliferative efficacy of NK cells, effectively prime NK cell clusters produced increased interferon-gamma, especially in the early culture periods. In conclusion, the present study demonstrates that our novel lipid conjugates could serve as a promising alternative for future NK cell mass production.