Najmina Mazaya, Kobayashi Shingo, Shimazui Rena, Takata Haruka, Shibata Mayuka, Ishibashi Kenta, Kamizawa Hiroshi, Kishimura Akihiro, Shiota Yoshihito, Ida Daichi, Shimizu Taro, Ishida Tatsuhiro, Katayama Yoshiki, Tanaka Masaru, Mori Takeshi
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Motooka 819-0395, Japan.
Institute for Materials Chemistry and Engineering, Kyushu University, Motooka 819-0395, Japan.
Pharmaceutics. 2024 Sep 28;16(10):1271. doi: 10.3390/pharmaceutics16101271.
Acrylamide polymers with zwitterionic carboxybetaine (CB) side groups have attracted attention as stealth polymers that do not induce antibodies when conjugated to proteins. However, they induce antibodies when modified onto liposomes. We hypothesized that antibodies are produced against polymer backbones rather than CB side groups. In this study, we designed and synthesized a polymer employing CB in its main chain, poly(-acetic acid--methyl-propyleneimine) (PAMPI), and evaluated the blood retention of PAMPI-modified liposomes in mice. The non-fouling nature of PAMPI-modified liposomes estimated from serum protein adsorption was found to be not inferior to PCB- and PEG-modified liposomes. However, to our surprise, the PAMPI-modified liposomes showed an instantaneous clearance less than 1 h post-injection, comparable to the naked liposomes. The extent of the blood retention of polymer-modified liposomes cannot be predicted by their susceptibility to serum protein adsorption and semi-flexible conformation.
带有两性离子羧基甜菜碱（CB）侧基的丙烯酰胺聚合物作为隐形聚合物受到关注，这类聚合物与蛋白质偶联时不会诱导抗体产生。然而，当它们修饰到脂质体上时会诱导抗体产生。我们推测抗体是针对聚合物主链而非CB侧基产生的。在本研究中，我们设计并合成了一种在主链中采用CB的聚合物，聚（-乙酸--甲基-丙烯亚胺）（PAMPI），并评估了PAMPI修饰的脂质体在小鼠体内的血液滞留情况。从血清蛋白吸附估计，PAMPI修饰的脂质体的抗污性能不逊色于PCB和PEG修饰的脂质体。然而，令我们惊讶的是，PAMPI修饰的脂质体在注射后不到1小时就出现了瞬时清除，与裸脂质体相当。聚合物修饰的脂质体的血液滞留程度不能通过其对血清蛋白吸附的敏感性和半柔性构象来预测。
