pH‐Sensitive Magnetic Nanoparticle‐Mediated Natural‐Killer‐Cell‐Based Microrobots for Dual‐Targeted Delivery and Induction of Pro‐Inflammatory Macrophage Polarization

Author:

Nguyen Van Du12ORCID,Park Jieun3,Choi Seoyeon3,Nguyen Kim Tien2,Kim Hyungwoo3ORCID,Park Jong‐Oh2ORCID,Choi Eunpyo14ORCID

Affiliation:

1. Robot Research Initiative Chonnam National University 77 Yongbong‐ro Buk‐gu Gwangju 61186 Korea

2. Korea Institute of Medical Microrobotics 43‐26, Cheomdangwagi‐ro 208‐beon‐gil, Buk‐gu Gwangju 61011 Korea

3. School of Polymer Science and Engineering Chonnam National University 77 Yongbong‐ro, Buk‐gu Gwangju 61186 Korea

4. School of Mechanical Engineering Chonnam National University 77 Yongbong‐ro, Buk‐gu Gwangju 61186 Korea

Abstract

Adoptive cell therapy using natural killer (NK) cells emerges as the next‐generation cancer immunotherapy. Based on the intrinsic capability of direct cancer cell necrosis without prior education, a chemotherapeutic, free‐drug delivery, NK‐cell‐based platform can be developed. However, weak targeting of NK cells to solid tumors is observed. In addition, to boost the tumor‐killing efficiency, another immune‐regulating function should be added to the cells. Herein, a NK‐cell‐based hybrid system (NK‐Robot) conjugated with magnetic nanoparticles (MNPs) that provides 1) efficient guidance of NK cells and 2) targeted delivery of MNPs in situ is demonstrated, taking advantage of a newly designed, stimuli‐responsive polymeric linker. Thus, NK cells are allowed to target tumors under magnetic control conditions, and the liberated MNPs effectively reeducate the tumor‐associated macrophages (M2) to antitumor macrophages (M1), beneficial for the immunotherapy of tumors. In vivo experiments on BALB/c nude mice further support the finding that NK‐Robots effectively inhibit tumor growth.

Funder

National Research Foundation of Korea

Publisher

Wiley

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