PDF(Pubmed)
Abstract：
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.
摘要：
小分子荧光团经常面临诸如血液半衰期短等挑战，有限的物理化学和光学稳定性，和不良的药代动力学。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）缀合，创建HSA-ZW800-PEG。这种共轭显着改善了化学，物理，和生理条件下的光学稳定性，解决小分子在生物应用中经常遇到的问题。此外,HSA-ZW800-PEG的高分子量和消光系数通过增强的渗透性和保留作用增强了生物分布和肿瘤靶向性。独特的分布和消除动力学，随着HSA-ZW800-PEG的血液半衰期显着延长，有助于提高皮下和原位异种移植瘤动物模型的肿瘤靶向性。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。我们的研究指导了靶向显像剂和药物递送系统的进一步开发和优化。
