Preparation of Inert Polystyrene Latex Particles as MicroRNA Delivery Vectors by Surfactant-Free RAFT Emulsion Polymerization

Abstract

Permanent WRAP URL:http://wrap.warwick.ac.uk/83846 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. Publisher's statement:This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © American Chemical Society after peer review and technical editing by the publisher.To access the final edited and published work see http://dx.doi.org/10.1021/acs.biomac.5b01633 A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP url' above for details on accessing the published version and note that access may require a subscription. AbstractWe present the preparation of 11 nm polyacrylamide-stabilised polystyrene latex particles for conjugation to a microRNA model by surfactant-free RAFT emulsion polymerisation. Our synthetic strategy involved the preparation of amphiphilic polyacrylamide-block-polystyrene copolymers, which were able to self-assemble into polymeric micelles and 'grow' into polystyrene latex particles. The surface of these sterically stabilised particles was postmodified with a disulfide-bearing linker for the attachment of the microRNA model, which can be released from the latex particles under reducing conditions. These nanoparticles offer the advantage of ease of preparation via a scaleable process, and the versatility of their synthesis makes them adaptable to a range of applications.

Fluorescent Labeling and Biodistribution of Latex Nanoparticles Formed by Surfactant‐Free RAFT Emulsion Polymerization

“…For such application, the nanoparticles would only be required to cross the cellular membrane to reach the target site, without the need to cross the nuclei barrier. The reversible covalent decoration of such particles using miRNA was previously described by our group …”

“…In vitro cellular uptake was investigated using the human renal proximal tubular cell line (HK2) model for uptake and localization studies through fluorescent live‐cell imaging. HK2 cells were used as models in light of our previous study on miRNA delivery to HK2 cells by nanoparticles, as a mean to decrease the production of fibronectin, which plays a key role in the development of renal fibrosis . Using in vivo fluorescent imaging, bio‐distribution of 22 nm labeled particles was probed using a mouse model and the accumulation of these fluorescent particles in mouse organs was then examined via ex vivo imaging.…”

Heparin‐Mimicking Sulfonated Polymer Nanoparticles via RAFT Polymerization‐Induced Self‐Assembly

“…NP's designed with advanced controlled radical polymerization techniques such as reversible addition–fragmentation chain transfer mediated (RAFT) polymerization‐induced self‐assembly (PISA) can be exploited to overcome these challenges . PISA is typically performed through chain extension of a solvophilic macro‐RAFT agent with either a solvophilic monomer which when polymerized becomes solvophobic (RAFT dispersion polymerization) or a solvophobic monomer (RAFT emulsion polymerization) . This results in the formation of sterically stabilized, diblock copolymer core–shell NPs, where the particle surface is decorated with the solvophilic block of the stabilizing macro‐RAFT agent.…”

“…reported PISA using a galactose functional monomer to enhance delivery of a model drug via cell surface lectin binding . We have recently reported synthesis of polyacrylamide coated NPs via RAFT emulsion polymerization, and their use as micro‐RNA vectors and their in vivo biodistribution . Outside of biological applications, Armes and coworkers recently reported the synthesis of sulfated NPs via PISA both in dispersion and emulsion to further understand NP occlusion in calcite and zinc oxide crystals .…”

RAFT Emulsion Polymerization as a Platform to Generate Well‐Defined Biocompatible Latex Nanoparticles

“…Whereas, Wang and coworkers used RAFT emulsion polymerization to control the monomer composition of the nanoparticle shell, yielding a system of which the release rate of a model hydrophobic drug (indomethacin) could be tuned with pH . Furthermore, our group has illustrated the potential for surface modification of polyacrylamide stabilized polystyrene nanoparticles synthesized from RAFT emulsion, initially as micro‐RNA carriers, and also for fluorescent labeling for studies in vitro and in vivo . In addition, we recently used this approach to generate well‐defined mannose coated nanoparticles able to interact with lectin Concanavalin A .…”