Zhou Min, Cui Ruxin, Luo Zhengjie, Cong Zihao, Shao Ning, Yuan Ling, Gu Jiawei, He Hongyan, Liu Runhui
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
J Funct Biomater. 2023 Jul 21;14(7):382. doi: 10.3390/jfb14070382.
Polyethylene glycol (PEG)-doxorubicin (DOX) conjugation is an important strategy to improve toxicity and enhance clinically therapeutic efficacy. However, with the frequent use of PEG-modified drugs, the accumulation of anti-PEG antibodies has become a tough issue, which limits the application of PEG-drug conjugation. As an alternative solution, poly(2-oxazoline) (POX)-DOX conjugation has shown great potential in the anti-tumor field, but the reported conjugation process of POX with DOX has drawbacks such as complex synthetic steps and purification. Herein, we propose a convenient and controllable strategy for the synthesis of POX-DOX conjugation with different chain lengths and narrow dispersity by -boc-2-bromoacetohydrazide-initiated 2-ethyl-oxazoline polymerization and the subsequent deprotection of the -Boc group and direct reaction with DOX. The DOX-PEtOx conjugates were firstly purified, and the successful conjugations were confirmed through various characterization methods. The synthetic DOX-PEtOx conjugates reduce the toxicity of DOX and increase the selectivity to tumor cells, reflecting the promising application of this POX-DOX conjugation strategy in drug modification and development.
聚乙二醇（PEG）-阿霉素（DOX）偶联是提高毒性和增强临床治疗效果的重要策略。然而，随着PEG修饰药物的频繁使用，抗PEG抗体的积累已成为一个棘手的问题，这限制了PEG-药物偶联物的应用。作为一种替代解决方案，聚（2-恶唑啉）（POX）-DOX偶联在抗肿瘤领域显示出巨大潜力，但报道的POX与DOX的偶联过程存在合成步骤复杂和纯化困难等缺点。在此，我们提出了一种简便且可控的策略，通过 -boc-2-溴乙酰肼引发2-乙基恶唑啉聚合，随后对 -Boc基团进行脱保护并与DOX直接反应，合成具有不同链长和窄分散度的POX-DOX偶联物。首先对DOX-PEtOx偶联物进行纯化，并通过各种表征方法确认成功偶联。合成的DOX-PEtOx偶联物降低了DOX的毒性并提高了对肿瘤细胞的选择性，反映了这种POX-DOX偶联策略在药物修饰和开发中的应用前景。
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