通过巯基介导的摄取实现聚胍的可控二硫键交换聚合及其在生物医学中的有效应用。
Controllable Disulfide Exchange Polymerization of Polyguanidine for Effective Biomedical Applications by Thiol-Mediated Uptake.
机构信息
State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education) and Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.
出版信息
Angew Chem Int Ed Engl. 2022 Jun 7;61(23):e202200535. doi: 10.1002/anie.202200535. Epub 2022 Apr 5.
New preparation methods of vectors are the key to developing the next generation of biomacromolecule delivery systems. In this study, a controllable disulfide exchange polymerization was established to obtain low-toxicity and efficient bioreducible polyguanidines (mPEG -b-PSS , n=13, 26, 39, 75, 105) by regulating the concentration of activated nucleophiles and reaction time under mild reaction conditions. The relationship between the degrees of polymerization and biocompatibility was studied to identify the optimal polyguanidine mPEG -b-PSS . Such polyguanidine exhibited good in vitro performance in delivering different functional nucleic acids. The impressive therapeutic effects of mPEG -b-PSS were further verified in the 4T1 tumor-bearing mice as well as the mice with full-thickness skin defects. Controllable disulfide exchange polymerization provides an attractive strategy for the construction of new biomacromolecule delivery systems.
新型载体的制备方法是开发下一代生物大分子输送系统的关键。在本研究中，建立了一种可控的二硫键交换聚合反应，通过调节温和反应条件下的活化亲核试剂的浓度和反应时间，获得低毒性和高效的生物还原型聚胍（mPEG-b-PSS，n=13、26、39、75、105）。研究了聚合度与生物相容性之间的关系，以确定最佳的聚胍 mPEG-b-PSS。这种聚胍在输送不同功能核酸方面表现出良好的体外性能。mPEG-b-PSS 的显著治疗效果在 4T1 荷瘤小鼠和全层皮肤缺损小鼠中也得到了进一步验证。可控的二硫键交换聚合反应为构建新型生物大分子输送系统提供了一种有吸引力的策略。
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