Controlling Cellular Uptake and Toxicity of Polyphenylene Dendrimers by Chemical Functionalization

Abstract

Polyphenylene dendrimers (PPDs) represent a unique class of macromolecules based on their monodisperse and shape-persistent nature. These characteristics have enabled the synthesis of a new genre of "patched" surface dendrimers, where their exterior can be functionalized with a variety of polar and nonpolar substituents to yield lipophilic binding sites in a site-specific way. Although such materials are capable of complexing biologically relevant molecules, show high cellular uptake in various cell lines, and low to no toxicity, there is minimal understanding of the driving forces to these characteristics. We investigated whether it is the specific chemical functionalities, relative quantities of each moiety, or the "patched" surface patterning on the dendrimers that more significantly influences their behavior in biological media.

Neurotoxicity of Nanomaterials: An Up-to-Date Overview

“…Depending on their physicochemical characteristics, such as surface chemistry, surface charge, and size, dendrimers have been shown to induce several neurotoxicological responses inside the organism [81].…”

Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

“…As lipophilic residues, propyl chains were selected due to their performance in a previous in vitro screening that analyzed the influence of various nonpolar substituents (i.e., phenyl, propyl, iso propyl, butyl, and hexyl chains) on the cell uptake and toxicity of PPDs. 20 1,3,6,8-Tetraethynylpyrene served as the dendrimer core so that the blue emission of pyrene could be used as a fluorescence probe to enable monitoring of the macromolecules via fluorescence microscopy. PPDs with different but precisely established numbers and orientations of the sulfonic acid/ n -propyl surface groups were synthesized by reacting the core with functionalized cyclopentadienone building blocks in Diels–Alder cycloadditions.…”

Expanding the limits of synthetic macromolecular chemistry through Polyphenylene Dendrimers

“…While these results were very encouraging, it was still necessary to understand the fundamental forces behind the high cell uptake and low toxicity of patched surface dendrimers, so a series of experiments were designed to observe the influence and the type and relative ratios of the polar and nonpolar groups. First- and second-generation dendrimers were synthesized with sulfonic, carboxylic, or phosphonic acids as the polar group, and n-propyl, butyl, hexyl, or isopropyl chains as the nonpolar functionality to observe the influence of the type of chemical modification (Hammer et al 2017 ). Additionally, PPDs were synthesized with either a 1:1 or 2:1 ratio of polar/nonpolar groups (i.e., two sulfonic acids per one propyl chain) to investigate how the relative ratio influences their properties.…”