Synthesis, Characterization, and In Vitro Properties of Zwitterionic Dendrimers with a Reactive Focal Functionality for Biomedical Applications

作者：Mingxuan Zhang, Masoud Zamani, Yuan Su, Ashley Miles, Ziwen Zhang, Emmanuel M. Nsengiyumva, Scott M. Grayson, Yun Wu, Chong Cheng · 发表于：Langmuir · 年份：2025 · DOI：10.1021/acs.langmuir.5c02200 · 被引用次数：1 · 研究领域：Dendrimers and Hyperbranched Polymers、RNA Interference and Gene Delivery、Advanced biosensing and bioanalysis techniques

As novel, well-defined, highly branched macromolecules with numerous superhydrophilic terminal groups, zwitterionic dendrimers (ZDs) are expected to possess charge-neutral outer layers, which can be highly hydrated to exhibit superior antifouling properties and minimized undesirable interactions within biological systems. The incorporation of ZDs with degradable structures and reactive functionality can further expand their applicability. Here, we present the design, synthesis, characterization, and in vitro properties of such ZDs carrying quantitatively one reactive group at the focal point. The ZDs were prepared by divergent synthesis using an azido-functionalized diene core molecule for alternating thiol–ene and esterification reactions, followed by the last functionalization step using a sulfobetaine (SB)-containing thiol. The resulting ZDs had hydrolyzable ester-based inner domains, numerous SB-based terminals to ensure zwitterionic properties, and an azido focal functionality that may be employed for further conjugation of ZDs with biomedical moieties or therapeutic systems. Their chemical structures were verified by 1 H NMR analysis. Their molecular weights and structural integrity were characterized by matrix-assisted laser desorption ionization and time-of-flight mass spectrometry (MALDI-TOF MS). Dye could be incorporated into the ZD molecules using a small amount of dye-based thiol in the last functionalization step. In vitro studies revealed noncytotoxicity at 1000...