State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300350, P. R. China.
University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713, AV, Groningen, The Netherlands.
Angew Chem Int Ed Engl. 2021 Aug 2;60(32):17714-17719. doi: 10.1002/anie.202106329. Epub 2021 Jul 1.
A lipid named DCPA was synthesized under microwave-assisted heating. DCPA possesses a pyridine betaine, hydrophilic group that can be complexed with water through hydrogen bonding (DCPA-H O). DCPA-H O liposomes became protonated relatively fast already at pH<6.8, due to the high HOMO binding energy of DCPA-H O. In murine models, DCPA-H O liposomes had longer blood circulation times than natural DPPC or cationic DCPM liposomes, while after tail-vein injection DCPA-H O liposomes targeted faster to solid tumors and intra-abdominal infectious biofilms. Therapeutic efficacy in a murine, infected wound-healing model of tail-vein injected ciprofloxacin-loaded DCPA-H O liposomes exceeded the ones of clinically applied ciprofloxacin as well as of ciprofloxacin-loaded DPPC or DCPM liposomes.
一种名为 DCPA 的脂质在微波辅助加热下合成。DCPA 具有吡啶甜菜碱亲水基团，可通过氢键与水形成复合物（DCPA-H O）。由于 DCPA-H O 的 HOMO 结合能较高，因此在 pH<6.8 时，DCPA-H O 脂质体已经能够快速质子化。在小鼠模型中，与天然 DPPC 或阳离子 DCPM 脂质体相比，DCPA-H O 脂质体具有更长的血液循环时间，而尾静脉注射后，DCPA-H O 脂质体更快地靶向实体瘤和腹内感染性生物膜。在尾静脉注射载有环丙沙星的 DCPA-H O 脂质体的感染性伤口愈合模型的小鼠中，其治疗效果优于临床应用的环丙沙星以及载有 DPPC 或 DCPM 的环丙沙星脂质体。
