Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.
Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.
Nanomedicine. 2019 Oct;21:102058. doi: 10.1016/j.nano.2019.102058. Epub 2019 Jul 22.
Albumin is a serum transport protein, which has been utilized as a carrier for a variety of drugs to improve their delivery efficiency and to obtain favorable pharmacokinetic profiles. However, natural albumin possesses only a few high-affinity binding sites for a limited number of drugs. This results in deficiencies in drug-loading and serum stability, and consequently, in impaired therapeutic efficacy. Herein, BSA was modified with different isothiocyanate conjugates (BSA-ITCs), which self-assembled with paclitaxel (PTX) to produce BSA-ITCs/PTX nanoparticles. Among these BSA-ITCs, phenethyl isothiocyanate (PEITC)-modified BSA (BSA-PEITC35) conjugates effectively loaded PTX and formed highly stable BSA-PEITC35/PTX nanoparticles. Molecular modeling studies suggested that PEITC groups in BSA-PEITC35 can significantly lower the PTX binding free energy. BSA-PEITC35/PTX showed enhanced stability, prolonged blood circulation and increased tumor accumulation than unmodified BSA/PTX, and exerted more potent antitumor activity than both BSA/PTX and Abraxane in subcutaneous mouse tumor models after intravenous administration.
白蛋白是一种血清转运蛋白，已被用作多种药物的载体，以提高其递送效率并获得有利的药代动力学特征。然而，天然白蛋白对有限数量的药物仅有少数高亲和力结合位点。这导致载药量和血清稳定性不足，从而降低了治疗效果。本文中，通过不同的异硫氰酸酯（BSA-ITCs）对 BSA 进行了修饰，这些异硫氰酸酯与紫杉醇（PTX）自组装形成了 BSA-ITCs/PTX 纳米粒。在这些 BSA-ITCs 中，苯乙基异硫氰酸酯（PEITC）修饰的 BSA（BSA-PEITC35）缀合物有效负载了 PTX 并形成了高度稳定的 BSA-PEITC35/PTX 纳米粒。分子建模研究表明，BSA-PEITC35 中的 PEITC 基团可以显著降低 PTX 的结合自由能。与未修饰的 BSA/PTX 相比，BSA-PEITC35/PTX 具有更高的稳定性、更长的血液循环时间和更高的肿瘤蓄积，在静脉给药的皮下小鼠肿瘤模型中，其抗肿瘤活性也强于 BSA/PTX 和 Abraxane。
