Synthesis and characterization of dendritic star-shaped zwitterionic polymers as novel anticancer drug delivery carriers

In this work, a novel dendritic star-shaped zwitterionic polymer, polyamidoamine-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] (PAMAM-g-PDMAPS), was synthesized. PAMAM dendrimers (generation 2, G2) were firstly prepared and then converted into the PAMAM-Br macroinitiator with 2-bromoisobutyryl bromide for ATRP. Finally, ATRP of zwitterionic DMAPS was carried out to obtain the dendritic star-shaped polymers PAMAM-g-PDMAPS with different PDMAPS chain lengths. Fourier transform-infrared spectroscopy, (1)H NMR, dynamic laser light scattering (DLS), and TEM were used to characterize the polymers. Encapsulation of adriamycin (ADR) by PAMAM-g-PDMAPS nanoparticles and ADR release behavior from ADR-loaded PAMAM-g-PDMAPS nanoparticles were investigated in detail. PAMAM-g-PDMAPS polymers, even starting from low-generation PAMAM core (G2), were found to show high loading efficiency for ADR because ADR existed not only within G2 PAMAM cores but also in PDMAPS layers. The release profile of ADR from ADR-loaded PAMAM-g-PDMAPS nanoparticles was pH-sensitive and could be controlled by the length of PDMAPS chains. Cell viability studies indicated that ADR-loaded PAMAM-g-PDMAPS could effectively restrain the growth of HepG2 cells and even kill them, whereas PAMAM-g-PDMAPS exhibited nontoxicity. All these results demonstrated that dendritic star-shaped zwitterionic polymers PAMAM-g-PDMAPS are attractive candidates as anticancer drug delivery carriers.