정은지 (University of Southern California) | 한빛사논문 > 한빛사

한빛사논문

조회253

University of Southern California

CV File 355 kb

ACS Nano, Jan 11 2024, | https://doi.org/10.1021/acsnano.3c09201 MRI Detection of Lymph Node Metastasis through Molecular Targeting of C-C Chemokine Receptor Type 2 and Monocyte Hitchhiking

Noah Trac ¹, Zixi Chen ¹, Hyun-Seok Oh ¹, Leila Jones ¹, Yi Huang ¹, Joshua Giblin ¹, Mitchell Gross ^2,3, Naomi S Sta Maria ⁴, Russell E Jacobs ⁴, Eun Ji Chung^{1,3,5,6,7,8,9}

¹Department of Biomedical Engineering, University of Southern California, Los Angeles, California 90089, United States.

²Lawrence J. Ellison Institute for Transformative Medicine, Los Angeles, California 90064, United States.

³Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, United States.

⁴Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute and Keck School of Medicine, University of Southern California, Los Angeles, California 90033, United States.

⁵Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, United States.

⁶Department of Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, United States.

⁷Department of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, United States.

⁸Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, United States.

⁹Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089, United States.

Corresponding Author : Eun Ji Chung

Abstract

Biopsy is the clinical standard for diagnosing lymph node (LN) metastasis, but it is invasive and poses significant risk to patient health. Magnetic resonance imaging (MRI) has been utilized as a noninvasive alternative but is limited by low sensitivity, with only ∼35% of LN metastases detected, as clinical contrast agents cannot discriminate between healthy and metastatic LNs due to nonspecific accumulation. Nanoparticles targeted to the C-C chemokine receptor 2 (CCR2), a biomarker highly expressed in metastatic LNs, have the potential to guide the delivery of contrast agents, improving the sensitivity of MRI. Additionally, cancer cells in metastatic LNs produce monocyte chemotactic protein 1 (MCP1), which binds to CCR2 ⁺ inflammatory monocytes and stimulates their migration. Thus, the molecular targeting of CCR2 may enable nanoparticle hitchhiking onto monocytes, providing an additional mechanism for metastatic LN targeting and early detection. Hence, we developed micelles incorporating gadolinium (Gd) and peptides derived from the CCR2-binding motif of MCP1 (MCP1-Gd) and evaluated the potential of MCP1-Gd to detect LN metastasis. When incubated with migrating monocytes in vitro, MCP1-Gd transport across lymphatic endothelium increased 2-fold relative to nontargeting controls. After administration into mouse models with initial LN metastasis and recurrent LN metastasis, MCP1-Gd detected metastatic LNs by increasing MRI signal by 30-50% relative to healthy LNs. Furthermore, LN targeting was dependent on monocyte hitchhiking, as monocyte depletion decreased accumulation by >70%. Herein, we present a nanoparticle contrast agent for MRI detection of LN metastasis mediated by CCR2-targeting and demonstrate the potential of monocyte hitchhiking for enhanced nanoparticle delivery.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-24)
연구진국외 연구진
분야

댓글 작성 로그인

CV 열람하기

연락처 보기