HSA-ZW800-PEG for Enhanced Optophysical Stability and Tumor Targeting

Paul Jang; Jinhui Ser; Kevin Cardenas; Hajin Joanne Kim; Morgan Hickey; Jiseon Jang; Jason Gladstone; Aisha Bailey; Jason Dinh; Vy Nguyen; Emma DeMarco; Surbhi Srinivas; Homan Kang; Satoshi Kashiwagi; Kai Bao; Atsushi Yamashita; Hak Soo Choi

doi:10.3390/ijms25010559

International Journal of Molecular Sciences (Dec 2023)

HSA-ZW800-PEG for Enhanced Optophysical Stability and Tumor Targeting

Paul Jang,
Jinhui Ser,
Kevin Cardenas,
Hajin Joanne Kim,
Morgan Hickey,
Jiseon Jang,
Jason Gladstone,
Aisha Bailey,
Jason Dinh,
Vy Nguyen,
Emma DeMarco,
Surbhi Srinivas,
Homan Kang,
Satoshi Kashiwagi,
Kai Bao,
Atsushi Yamashita,
Hak Soo Choi

Affiliations

Paul Jang: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Jinhui Ser: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Kevin Cardenas: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Hajin Joanne Kim: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Morgan Hickey: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Jiseon Jang: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Jason Gladstone: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Aisha Bailey: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Jason Dinh: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Vy Nguyen: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Emma DeMarco: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Surbhi Srinivas: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Homan Kang: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Satoshi Kashiwagi: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Kai Bao: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Atsushi Yamashita: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA
Hak Soo Choi: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA

DOI: https://doi.org/10.3390/ijms25010559
Journal volume & issue: Vol. 25, no. 1
p. 559

Abstract

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Small molecule fluorophores often face challenges such as short blood half-life, limited physicochemical and optical stability, and poor pharmacokinetics. To overcome these limitations, we conjugated the zwitterionic near-infrared fluorophore ZW800-PEG to human serum albumin (HSA), creating HSA-ZW800-PEG. This conjugation notably improves chemical, physical, and optical stability under physiological conditions, addressing issues commonly encountered with small molecules in biological applications. Additionally, the high molecular weight and extinction coefficient of HSA-ZW800-PEG enhances biodistribution and tumor targeting through the enhanced permeability and retention effect. The unique distribution and elimination dynamics, along with the significantly extended blood half-life of HSA-ZW800-PEG, contribute to improved tumor targetability in both subcutaneous and orthotopic xenograft tumor-bearing animal models. This modification not only influences the pharmacokinetic profile, affecting retention time and clearance patterns, but also enhances bioavailability for targeting tissues. Our study guides further development and optimization of targeted imaging agents and drug-delivery systems.

Published in International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General); Science: Chemistry
Website: http://www.mdpi.com/journal/ijms

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