pH-Responsive Hyperbranched Polymer Scaffolds for Polymer and Peptide Conjugation through Molecular Recognition: Synthesis and Self-Assembly

Hyperbranched polymers can be suitable polymeric scaffolds for the modification of functional groups and fabrication of applicable nanoparticles considering their good solubility, numerous modification sites, and unique self-assembly behaviors. To facilitate the modification process and obtain various functional hyperbranched polymers, a new inimer 2-((adamantan-1-yl)amino)-1-(4-((2-bromo-2-methylpropanoyl)oxy)phenyl)-2-oxoethyl methacrylate (ABMA) with an adamantyl group was prepared in this research through the Passerini reaction. ABMA was copolymerized with 2-(diisopropylamino)ethyl methacrylate (DPA), affording the pH-responsive hyperbranched polymer hPDPA. Model molecules poly(ethylene glycol) (PEG) and the peptide RRRRRRRRC (PArg) with a cell-penetrating octaarginine fragment were conjugated with β-cyclodextrin (β-CD) to modify the hPDPA through molecular recognition. The inclusion complex hPDPA/PEG self-assembled into micelles in phosphate buffer at pH 7.4, while hPDPA/PEG/PArg self-assembled into vesicles because of the repulsion of the positively charged PArg. It was demonstrated that the DOX-loaded hPDPA/PEG/PArg could be internalized by Hela cells with high efficiency and could induce apoptosis of Hela cells.