Synthesis of Customizable Macromolecular Conjugates as Building Blocks for Engineering Metal–Phenolic Network Capsules with Tailorable Properties

Abstract

Metal−phenolic networks (MPNs), formed through coordination bonding between phenolic molecules and metal ions, are a promising class of materials for engineering particle systems for diverse applications. However, the properties of such MPNs are inherently restricted due to the finite properties of naturally occurring phenolic molecules. Herein, we report a simple and robust approach to incorporate phenolic moieties into polymers, thereby providing customizable phenolic ligand building blocks that can be used to assemble capsules with a range of tailorable properties. The phenolic ligand building blocks were synthesized via carbonic anhydride coupling to terminal amines, a conjugation approach typically used for peptide coupling but applied herein for functionalizing polymers. The chemistry enabled optimized end-group purity, thus affording a robust and efficient strategy to generate a library of macromolecular poly(ethylene glycol) (PEG) catechol building blocks with different architectures (i.e., 2-, 4-, and 8-arm) and molecular weights (from 2.5 to 20 kDa). The resulting phenolic building blocks were applied to fabricate capsules with shell thickness, permeability, and cell association properties that were controlled via the variation of the macromolecular catechol architecture and molecular weight. Specifically, the shell thickness was varied more than 19fold (i.e., between ∼9 and 169 nm) by judicious selection of the polymer molecular weight, arm number, and template. Similarly, the permeability of the resulting MPN capsules to 500 kDa dextran was tuned from >90 to <5% by varying the number of arms in the polymer structure while maintaining a constant PEG M n -to-catechol group ratio. Furthermore, the cell association was reduced by a factor of 2.5 by employing 20 kDa 8-arm PEG instead of 2.5 kDa 2-arm PEG during film assembly. These results demonstrate that the applied macromolecular conjugation approach can be used to customize particle properties, potentially facilitating applications in therapeutic delivery, imaging, separations, and catalysis.

Macromolecular Engineering of Thermoresponsive Metal–Phenolic Networks

“…The observed annular fluorescence of the capsules likely originates from hydrogen bonding interactions between dextran and the PNIPAM film, leading to localization of the dextran in/on the capsule wall, which is consistent with previous observations. 51 In contrast, when the capsules were loaded with 500 kDa FITC-dextran and subsequently washed with MOPS buffer at a temperature below the LCST, a considerably lower loading efficiency was observed (i.e., a loading efficiency of 17% was obtained, which was lower than the loading efficiency obtained when encapsulation was performed at 50 °C). The faint fluorescence is likely derived from hydrogen bonding between the cargo molecules and the MPN film (Figure S21).…”

Engineering Programmable DNA Particles and Capsules Using Catechol-Functionalized DNA Block Copolymers

“…Protection strategies for the catechol moieties in the phenolic molecule were used to minimize side reactions of the aromatic hydroxyls. 12 Specifically, 3-(3,4-dihydroxyphenyl)propanoic acid (dihydrocaffeic acid, DHCA) was used as a source of catechol groups, and the hydroxyl groups were protected by iBoc (isobutyl carbonate) groups to yield DHCA carbonic anhydride, iBocDHCA. A catechol-functionalized monomer was subsequently obtained by coupling iBocDHCA to 2-hydroxyethyl methacrylate.…”

“…An acidic environment (i.e., 0.5 M HCl) is expected to revert coordination networks in MPNs to the monocomplex state. 12 A metal-chelating agent such as ethylenediaminetetraacetic acid (EDTA) can bind to the Fe III ions in the MPN, resulting in the disruption of the MPN. 1 Tween 20 and urea can hinder hydrophobic and hydrogen bonding interactions, respectively, within the DBC−Fe III MPN systems.…”

Surface Membrane Coating as a Versatile Platform for Modifying Antitumor Nanoparticles

“…153 However, mesoporous nanomaterials or assembling NPs may leak before reaching the tumor site, which, because of its network structure, natural phenolic and metal ions display significant nonspecific protein adsorption, 162 and a rapid and significant RES sequestration alters the MPNs pharmacokinetics, leading to shorter circulation and off-targeting characteristics. 130 As a result, many MPN membrane modification strategies have been proposed, including the use of ligands FA for targeting, 130 with the enhanced targeting specificity, 163 PEG allowing for antifouling properties, long blood circulation lifetimes, and high water solubility, 164 and Chitosan (CS), which could be conveniently introduced to MPN due to a strong affinity for negatively charged MPN membranes via electrostatic interaction. Mu et al designed a metal-polyphenol (MPN) embedded with CS membrane coating to deliver Cab for melanoma therapy.…”