Synthesis and self‐assembly of amphiphilic star‐block copolymers consisting of polyethylene and poly(ethylene glycol) segments

Abstract

We report on the synthesis and self-assembly in water of well-defined amphiphilic star-block copolymers with a linear crystalline polyethylene (PE) segment and two or three poly(ethylene glycol) (PEG) segments as the building blocks. Initially, alkynyl-terminated PE (PE-B) is synthesized via esterification of pentynoic acid with hydroxyl-terminated PE, which is prepared using chain shuttling ethylene polymerization with 2,6-bis[1-(2,6-dimethylphenyl) imino ethyl] pyridine iron (II) dichloride/methylaluminoxane/diethyl zinc and subsequent in situ oxidation with oxygen. Then diazido-and triazido-terminated PE (PE-(N 3 ) 2 and PE-(N 3 ) 3 ) are obtained by the click reactions between PE-B and coupling agents containing triazido or tetraazido, respectively. Finally, the three-arm and four-arm star-block copolymers, PE-b-(PEG) 2 and PE-b-(PEG) 3 , are prepared by click reactions between PE-(N 3 ) 2 or PE-(N 3 ) 3 and alkynyl-terminated PEG. The self-assembly of the resultant amphiphilic star-block copolymers in water was investigated by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. It is found that, in water, a solvent selectively good for PEG blocks; these star-block copolymer chains could self-assemble to form platelet-like micelles with insoluble PE blocks as crystalline core and soluble PEG blocks as shell. The confined crystallization of PE blocks in self-assembled structure formed in aqueous solution is investigated by differential scanning calorimetry.

Polymerization of Ethylene Oxide, Propylene Oxide, and Other Alkylene Oxides: Synthesis, Novel Polymer Architectures, and Bioconjugation

“…Click couplings, especially the copper-catalyzed azide–alkyne cycloaddition, but also thiol–ene and Diels–Alder reactions, have been identified as a convenient method to attach prefabricated PEG chains. − Since click reactions take place under mild conditions and tolerate a great amount of functional groups, they have found to be particularly useful for the preparation of miktoarm stars. − Controlled radical polymerization techniques, such as ARTP and RAFT, have also been explored extensively as a synthetic tool for arm-first star polymer synthesis. − After end functionalizing PEG with a suitable initiator group, cross-linking polymerization of divinyl monomers leads to star architectures. In analogy, ring-opening metathesis polymerization was applied using bis-norbonene monomers .…”

A High Loading and Recyclable Pentaerythritol Supported Imidazolidin-4-one Catalyst for Enantioselective Diels–Alder Reactions

“…Chiral imidazolidin-4-ones 1-2 [28,40] and pentaerythritol derivatives 3-5 [38,39] were prepared by the established procedure according to the corresponding literatures, respectively. Catalysts I-II can be obtained with good yield by the reaction between 3 or 4 with 1 in dry DMF in the presence of Cs 2 CO 3 .…”

Folate-Targeted Anticancer Drug Delivery via a Combination Strategy of a Micelle Complex and Reducible Conjugation

“…Cancer remains one of the malignant diseases that pose significant threats to human health. The polymer micelles self-assembled by amphiphilic block copolymers are one of the most investigated nanocarriers that can greatly improve the solubility and stability of the encapsulated drug in blood circulation and increase the accumulation of the drug in tumor tissues by the enhanced permeation and retention (EPR) effect. − To further promote the therapeutic efficiency and minimize the off-target side effects of nanocarriers, conjugation of various active targeting ligands to the surface of nanocarriers has been frequently adopted to realize specific recognition by the corresponding receptors localized on the membrane of the cancer cells. − Folic acid (FA) is one of the most used targeting ligands due to the overexpressed FA receptors in many cancer cell lines. − Recently, notable work on FA-targeted drug delivery is Elzoghby’s dual-targeted micelles for efficient hepatocellular carcinoma therapy in vivo. , However, conjugation of hydrophobic FA to the surface of nanocarriers usually alters the hydrophilic/hydrophobic balance of the stabilized nanoparticles, leading to their thermodynamic instability and subsequent formation of aggregates, which apparently compromises the in vivo long circulation and minimized side effects of nanocarriers. − The currently leading strategy to overcome this issue is to incorporate a protecting hydrophilic stealth that can be deshielded to expose the targeting ligand at the desired tumor site, which generally involves multistep chemical modifications, conjugations, and purifications. − To develop a simple alternative toward FA-mediated enhanced anticancer drug delivery, a combination strategy of mixed micelles and reducible conjugation was reported in this study. − FA was first conjugated to the terminus of the hydrophilic block of a reduction-sensitive miktoarm star-shaped amphiphilic copolymer, PCL 3 -SS-POEGMA 1 , with the previously optimized star structure by click coupling via a reducible disulfide link . The resulting PCL 3 -SS-POEGMA 1 -SS-FA was further mixed with the parent PCL 3 -SS-POEGMA 1 to afford a micelle complex with both reducibly conjugated and relatively low amount of FA-targeting ligands toward excellent FA-mediated targeted drug delivery without compromised salt stability, which was evaluated comprehensively in vitro and in vivo.…”