Work

Development of Natural Killer Cell–Drug Conjugates via Membrane-Installed Liposomes for Pancreatic Cancer Treatment

Year: 2025

Type: article

Abstract: Adoptive cell-based therapy has emerged as an innovative method for cancer treatment, capitalizing on the innate cytotoxicity of immune cells to eliminate tumors. Although chimeric-antigen-receptor-modified T and natural killer (NK) cells have demonstrated significant therapeutic potential, their clinical translation is hindered by the complex nature of genetic engineering, high production costs, and risks of severe immune-related adverse effects. Addressing these barriers, we present a biomaterial-based approach to engineering NK cells, entirely bypassing the need for genetic modification. Initially, we systematically evaluated the surface modification of NK cells by employing a range of dibenzocyclooctyne (DBCO)–lipid biomaterials based on 1,2-distearoyl- sn -glycero-3-phosphoethanolamine (DSPE) lipid: (a) 2 linear structures with different polyethylene glycol (PEG) chain lengths (DSPE-PEG2k-DBCO and DSPE-PEG5k-DBCO), (b) a tadpole structure (DSPE-PEG2k-Di-PEG2k-DBCO), and (c) a branched structure (DSPE-PEG2k-HA-DBCO). The tadpole-shaped DSPE-PEG2k-Di-PEG2k-DBCO exhibited remarkable membrane anchoring, biocompatibility, and preservation of membrane integrity and facilitated the subsequent conjugation of gemcitabine-loaded liposomes (GLipo) through DBCO–azide click chemistry, as validated using fluorescence microscopy. The fabricated GLipo-NK cell–drug conjugates maintained native NK cell viability (>80%) and enabled targeted drug release at tumor sites. Our GLipo-modified NK cells showed superior in vitro cytotoxicity against MIA PaCa-2 pancreatic cancer cells, attributed to a synergistic interaction between immune synapse formation and innate NK-cell-mediated cytotoxicity. This strategy establishes a robust framework for the development of safe, scalable, and effective cell-based immunotherapies aimed at treating solid tumors.

Source: Biomaterials Research

DOI: 10.34133/bmr.0285

Authors: Ashok Kumar Jangid, Chae Eun Lee, Minseon Ryu, Sungjun Kim, Kyobum Kim

Institution: Dongguk University

Language: English

Topic: Nanoparticle-Based Drug Delivery

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,700