PAMAM Dendrimers with an Oxyethylene Unit-Enriched Surface as Biocompatible Temperature-Sensitive Dendrimers

A novel type of temperature-sensitive dendrimer was synthesized using one-step terminal modification of polyamidoamine dendrimers (PAMAM) with various alkoxy diethylene glycols such as methoxy diethylene glycol, ethoxy diethylene glycol, and propoxy diethylene glycol. The obtained dendrimers exhibited tunable lower critical solution temperature (LCST), depending on PAMAM generation and terminal alkoxy groups. These dendrimers were shown to be taken up by HeLa cells through endocytosis and were trapped in intracellular compartments such as endosomes and lysosomes. Cellular uptake of the dendrimers was enhanced by increasing their incubation temperature above the LCST. In addition, the in vitro cytotoxicity of temperature-sensitive dendrimers at incubation temperatures below and above LCST was much lower than that of their parent PAMAM dendrimers. Results indicate that the dendrimers with oxyethylene unit-enriched surface might be promising to construct intelligent drug delivery systems.