Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02119, USA.
School of Materials Science & Engineering, Chonnam National University, Gwangju 61186, Republic of Korea.
Int J Mol Sci. 2023 Dec 31;25(1):559. doi: 10.3390/ijms25010559.
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.
小分子荧光团常常面临着一些挑战，如血液半衰期短、有限的物理化学和光学稳定性以及差的药代动力学特性。为了克服这些限制，我们将两性离子近红外荧光团 ZW800-PEG 与人血清白蛋白（HSA）结合，形成了 HSA-ZW800-PEG。这种结合显著提高了在生理条件下的化学、物理和光学稳定性，解决了小分子在生物应用中常见的问题。此外，HSA-ZW800-PEG 的高分子量和消光系数通过增强的通透性和保留效应增强了生物分布和肿瘤靶向性。独特的分布和消除动力学，以及 HSA-ZW800-PEG 的显著延长的血液半衰期，有助于提高皮下和原位异种移植荷瘤动物模型中的肿瘤靶向性。这种修饰不仅影响药代动力学特征，影响保留时间和清除模式，而且还增强了靶向组织的生物利用度。我们的研究为靶向成像剂和药物传递系统的进一步开发和优化提供了指导。
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