Magneto-Activation and Magnetic Resonance Imaging of Natural Killer Cells Labeled with Magnetic Nanocomplexes for the Treatment of Solid Tumors

Autor: Taehoon Sim, Alexander G. Ross, Dong-Hyun Kim, Kwang Soo Kim, Bongseo Choi, Hyunjun Choi, Soon Woo Kwon
Rok vydání: 2021
Předmět:
Zdroj: ACS Nano. 15:12780-12793
ISSN: 1936-086X
1936-0851
DOI: 10.1021/acsnano.1c01889
Popis: Natural killer (NK) cell-based immunotherapy has been considered a promising cell-based cancer treatment strategy with low side effects for early tumors and metastasis. However, the therapeutic efficacy is generally low in established solid tumors.iEx vivo/iactivation of NK cells with exogenous cytokines is often essential but ineffective to generate high doses of functional NK cells for cancer treatment. Image-guided local delivery of NK cells is also suggested for the therapy. However, there is a lack of noninvasive tools for monitoring NK cells. Herein, magnetic nanocomplexes are fabricated with clinically available materials (hyaluronic acid, protamine, and ferumoxytol; HAPF) for labeling NK cells. The prepared HAPF-nanocomplexes effectively attach to the NK cells (HAPF-NK). An exogenous magnetic field application effectively achieves magneto-activation of NK cells, promoting the generation and secretion of lytic granules of NK cells. The magneto-activated HAPF-NK cells also allow an MR image-guided NK cell therapy to treat hepatocellular carcinoma (HCC) solid tumors via transcatheter intra-arterial infusion. Suppressed tumor growth after the treatment of IA infused magneto-activated NK cells demonstrated a potential enhanced therapeutic efficacy of image guided local delivery of magneto-activated HAPF-NK cells. Given the potential challenges of NK cell cancer immunotherapy against established solid tumors, the effective NK cell labeling with HAPF, magneto-activation, and MRI contrast effect of NK cells will be beneficial to enhance the NK cell-therapeutic efficacy in various cancers.
Databáze: OpenAIRE