Two for the Price of One: PAMAM-Dendrimers with Mixed Phosphoryl Choline and Oligomeric Poly(Caprolactone) Surfaces

Abstract

The application of dendrimers for biological and medical purposes is highly dependent on the type of surface group in relation to cytotoxicity. Since amine terminated PAMAM dendrimers have been shown to have toxic properties and thereby limited applications in the medical field, the discovery of a new nontoxic surface coating is of great interest. In the present work, amine terminated DAB-PAMAM dendrimers from generation zero to four have been coated with statistical surface functionalization giving a dendrimer surface consisting of an approximately 1:1 mixture of zwitterionic phosphoryl choline hexanamide and 6-((6-hydroxyhexanoyl)oxy)hexanamide. The cytotoxic properties of generation two to four were tested on three different human cancer cell lines, SKBR3 human breast cancer cells, HeLa human cervical cancer cells, and Hep G2 human hepatocellular liver carcinoma cells and compared to the toxicity of amine terminated PAMAM dendrimers. In addition to lower cytotoxicity than observed for amine terminated dendrimers, the coated dendrimers showed minor cytotoxicity against all three human cell lines, negligible influence on ROS generation and mitochondrial membrane potential. These observations support the conclusion that the analyzed group of phosphorylcholine dendrimers may be suitable for medical applications.

Phosphocholine-Decorated PPI-Dendrimers Mimic Cell Membrane Phosphocholine Clusters and Tune the Innate Immune Activity of C-Reactive Protein

“…Dendrimer PPI generations 1–5 with primary amine groups at their surfaces were applied as scaffolds for multimeric presentation of PC. Dendrimers modified with PC groups by other synthetic routes have been reported previously. , However, fully derivatized dendrimer products have not been obtained. Here, we utilized the commercially available PC compound 2-methacryloyloxyethyl phosphorylcholine (MPC) to introduce PC groups onto the dendrimer surface amines.…”

Bisubstrate Ether‐Linked Uridine‐Peptide Conjugates as O‐GlcNAc Transferase Inhibitors

“…The linker benzyl 6‐hydroxyhexanoate was prepared from ϵ‐caprolactone over two steps in 90 % yield (SI) [20] . N ‐Acetylglucosamine was reacted with acetyl chloride to afford glycosyl chloride 6 in 70 % yield (SI) [21] .…”

Functionalization of Nanoparticulate Drug Delivery Systems and Its Influence in Cancer Therapy

“…Despite the widespread use of dendrimers in pharmaceutics and biomedicine, its complex basic features, such as toxicity due to the existence of a terminal NH2 group on the surface of dendrimer and fast clearing of dendrimer from the blood stream amid cancer treatment, restrain their function in the treatment of cancer [ 90 , 91 , 92 ]. Various studies have shown that the toxicity of dendrimers is influenced by their generation (size), development time, concentration, and the sort of terminal group on their exterior [ 93 , 94 , 95 , 96 ].…”