Kojima Chie, Hirata Rikuto, Dei Nanako, He Hao, Ikemoto Yuka, Matsumoto Akikazu
Department of Applied Chemistry, Graduate School of Engineering, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Department of Materials Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan.
Langmuir. 2025 Jan 21;41(2):1411-1417. doi: 10.1021/acs.langmuir.4c04276. Epub 2025 Jan 8.
Zwitterionic polymers exhibit strong hydration, high biocompatibility, and antifouling properties. Dendrimers are regularly branched polymers, which are used in the drug delivery system (DDS). In this study, we synthesized zwitterionic monomer- and polymer-conjugated dendrimers as a biocompatible nanoparticle to investigate the relation between the hydration property and biodistribution. A sulfobetaine monomer (SBM) was conjugated at the termini of the polyamidoamine (PAMAM) dendrimer. Polysulfobetaines (PSBs) were produced by reversible addition-fragmentation chain transfer polymerization and were also conjugated at the termini. Intermediate water, that is, water molecules loosely bound to the material, can be estimated from the melting peaks at less than 0 °C in differential scanning calorimetry (DSC) measurement. Our DSC results showed that the PSB-conjugated dendrimers (PSM-dens) contained more intermediate water than the SBM-conjugated dendrimer (SBM-den). PSB-dens accumulated in the tumor after intravenous administration, but SBM-den did not. These suggested that the amount of intermediate water, that is, the hydration property, was related to the biodistribution of the zwitterionic dendrimers. This relation is a possible design criterion for drug carriers. PSB-dens accumulated in the tumor even after the second injection, possibly overcoming the accelerated blood clearance observed with poly(ethylene glycol)-modified nanoparticles. Thus, this kind of zwitterionic polymer-conjugated dendrimer is useful for the DDS in cancer treatment.
两性离子聚合物具有很强的水合作用、高生物相容性和抗污性能。树枝状聚合物是规则分支的聚合物，用于药物递送系统（DDS）。在本研究中，我们合成了两性离子单体和聚合物共轭的树枝状聚合物作为生物相容性纳米颗粒，以研究水合性能与生物分布之间的关系。一种磺基甜菜碱单体（SBM）连接在聚酰胺胺（PAMAM）树枝状聚合物的末端。聚磺基甜菜碱（PSB）通过可逆加成-断裂链转移聚合制备，并同样连接在末端。中间水，即松散结合在材料上的水分子，可以通过差示扫描量热法（DSC）测量中低于0°C的熔融峰来估算。我们的DSC结果表明，PSB共轭树枝状聚合物（PSM-dens）比SBM共轭树枝状聚合物（SBM-den）含有更多的中间水。静脉注射后，PSB-dens在肿瘤中积累，但SBM-den没有。这些结果表明，中间水的量，即水合性能，与两性离子树枝状聚合物的生物分布有关。这种关系可能是药物载体的设计标准。即使在第二次注射后，PSB-dens仍在肿瘤中积累，可能克服了聚乙二醇修饰纳米颗粒所观察到的加速血液清除现象。因此，这种两性离子聚合物共轭树枝状聚合物可用于癌症治疗中的DDS。
