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

Abstract

Phenylboronic acid (PBA) has been highly acknowledged as a significant cancer recognition moiety in sialic acidoverexpressing cancer cells. In this investigation, lipid-mediated biomaterial integrated PBA molecules onto the surface of natural killer (NK) cells to make a receptor-mediated immune cell therapeutic module. Therefore, a 1,2-distearoyl-sn-glycero-3phosphorylethanolamine (DSPE) lipid-conjugated di−PEG−PBA (DSPE PEG -di(PEG−PBA) biomaterial was synthesized. The DSPE PEG -di(PEG−PBA) biomaterial exhibited a high affinity for sialic acid (SA), confirmed by fluorescence spectroscopy at pH 6.5 and 7.4. DSPE PEG -di(PEG−PBA) was successfully anchored onto NK cell surfaces (PBA-NK), and this biomaterial maintains intrinsic properties such as viability, ligand availability (FasL & TRAIL), and cytokine secretion response to LPS. The anticancer efficacy of PBA-NK cells was evaluated against 2D cancer cells (MDA-MB-231, HepG2, and HCT-116) and 3D tumor spheroids of MDA-MB-231 cells. PBA-NK cells exhibited greatly enhanced anticancer effects against SA-overexpressing cancer cells. Thus, PBA-NK cells represent a new anticancer strategy for cancer immunotherapy.

Networked Cluster Formation via Trigonal Lipid Modules for Augmented Ex Vivo NK Cell Priming

“…This approach enables the augmented NK cell activation without the requirement of additional supplementary cytokine cocktails. Our results demonstrated that (1) TL modules could be effectively immobilized into the lipid bilayers of NK cell membranes, specifically via hydrophobic interaction [33,34], and (2) they could strengthen the membrane connections of NK cells through material-mediated physical links. In consequence, as compared with naturally-driven NK clustering, which is mediated by ECM production (without the aid of biomaterials), a significant induction of multiple membrane interactions occurred, leading to rapid and tight formation of NK cell clusters, and effective cell priming ultimately took place, resulting in enhanced IFN-γ secretion in TLNK spheroids.…”