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

Ashok Kumar Jangid1, Chae Eun Lee1, Minseon Ryu1

  • 1Department of Chemical & Biochemical Engineering, Dongguk University, Seoul, Republic of Korea.

Biomaterials Research
|December 11, 2025
PubMed

Insights

This study introduces a novel biomaterial method to engineer natural killer (NK) cells for cancer therapy without genetic modification. This approach enhances NK cell drug delivery and boosts anti-tumor activity against solid tumors.

Area of Science:

  • Biomaterials Science
  • Immunology
  • Oncology

Background:

  • Adoptive cell therapy, using modified T cells or natural killer (NK) cells, shows promise for cancer treatment but faces challenges like complex genetic engineering, high costs, and adverse immune effects.
  • Current cell-based therapies often require genetic modification, increasing complexity and potential risks.

Purpose of the Study:

  • To develop a non-genetic biomaterial-based strategy for engineering NK cells to enhance their efficacy in treating solid tumors.
  • To evaluate various dibenzocyclooctyne (DBCO)-lipid biomaterials for NK cell surface modification and subsequent drug conjugation.

Main Methods:

  • Systematic evaluation of four DBCO-lipid biomaterials (DSPE-PEG2k-DBCO, DSPE-PEG5k-DBCO, DSPE-PEG2k-Di-PEG2k-DBCO, DSPE-PEG2k-HA-DBCO) for NK cell surface modification.
  • Conjugation of gemcitabine-loaded liposomes (GLipo) to modified NK cells using DBCO-azide click chemistry.
  • Assessment of NK cell viability, membrane integrity, and in vitro cytotoxicity against pancreatic cancer cells (MIA PaCa-2).

Main Results:

  • The tadpole-shaped DSPE-PEG2k-Di-PEG2k-DBCO biomaterial demonstrated superior membrane anchoring, biocompatibility, and preserved NK cell integrity.
  • Gemcitabine-loaded liposomes successfully conjugated to NK cells, forming GLipo-NK cell-drug conjugates with maintained NK cell viability (>80%).
  • GLipo-modified NK cells exhibited enhanced in vitro cytotoxicity against pancreatic cancer cells, suggesting a synergistic effect of immune synapse formation and NK cell activity.

Conclusions:

  • A non-genetic, biomaterial-based approach effectively engineers NK cells for targeted drug delivery and enhanced anti-tumor activity.
  • This strategy offers a promising framework for developing safer, scalable, and effective cell-based immunotherapies for solid tumors.
  • The developed GLipo-NK cell conjugates show potential for improved cancer treatment by combining targeted drug delivery with innate immune cell cytotoxicity.

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