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Disulfide-Functionalized Unimolecular Micelles as Selective Redox-Responsive Nanocarriers
KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Coating Technology.ORCID iD: 0000-0001-9035-4547
KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Coating Technology.
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2015 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602Article in journal (Refereed) Epub ahead of print
Abstract [en]

Redox-sensitive hyperbranched dendritic-linear polymers (HBDLPs) were prepared and stabilized individually as unimolecular micelles with diameters in the range 25–40 nm. The high molecular weight (500–950 kDa), core–shell amphiphilic structures were synthesized through a combination of self-condensing vinyl copolymerization (SCVCP) and atom transfer radical polymerization (ATRP). Cleavable disulfide bonds were introduced, either in the backbone, or in pendant groups, of the hyperbranched core of the HBDLPs. By triggered reductive degradation, the HBDLPs showed up to a 7-fold decrease in molecular weight, and the extent of degradation was tuned by the amount of incorporated disulfides. The HBDLP with pendant disulfide-linked functionalities in the hyperbranched core was readily postfunctionalized with a hydrophobic dye, as a mimic for a drug. An instant release of the dye was observed as a response to a reductive environment similar to the one present intracellularly. The proposed strategy shows a facile route to highly stable unimolecular micelles, which attractively exhibit redox-responsive degradation and cargo release properties.

Place, publisher, year, edition, pages
National Category
Polymer Chemistry
URN: urn:nbn:se:kth:diva-173310DOI: 10.1021/acs.biomac.5b00809OAI: diva2:852427

QP 201509

Available from: 2015-09-09 Created: 2015-09-09 Last updated: 2015-09-09Bibliographically approved
In thesis
1. Exploring Amphiphilic PEGMA-Based Architectures as Nanoparticles for Drug Delivery
Open this publication in new window or tab >>Exploring Amphiphilic PEGMA-Based Architectures as Nanoparticles for Drug Delivery
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Within the last decades, the stated potential of polymer constructs as drug delivery systems have challenged researchers to develop sophisticated polymers with tunable properties. The versatility of polymers makes them highly attractive to tailor nanoparticles (NPs) which fulfill the demands of effective drug delivery systems (DDS). The aim of this work was to design and synthesize amphiphilic ethylene glycol methacrylate-based (EGMA) macromolecules, and explore their potential as NPs for drug delivery.

Initially, a study of the controlled synthesis and solution properties of linear EGMA polymers, as well as the potential to transfer their behavior to amphiphilic comb copolymers, was conducted. Well-controlled polymers with interesting tunable thermo-responsive properties were accomplished by altering the monomer feed ratio. Furthermore, the comb copolymers formed self-assembled core-shell type structures in aqueous solution.

A library of amphiphilic fluorinated polymers was successfully established to explore the potential of EGMA-based polymers in a dual-functional theranostic delivery system. The non-toxic polymers self-assembled into small “stealthy” NPs, and the combination of fluorinated segments with EGMA segments allowed for detection by 19F-MRI with good imaging properties. The hydrophobic core of the NPs was capable to encapsulate and release an anti-cancer therapeutic, and effectively reduced the viability of three different cancer cell lines. The diffusion-controlled release kinetics of the drug from the NPs interestingly depended on the nature of the core moiety.

To reduce issues with instability of self-assembling NP systems the possibility to synthesize amphiphilic hyperbranched dendritic-linear polymers (HBDLPs) was investigated. Their three-dimensional structure was hypothesized to facilitate stabilization as unimolecular micelles. The architecture, hydrophilic/hydrophobic ratio, and high molecular weight showed to be crucial to avoid polymer association and stabilize the HBDLPs individually. In addition, the hyperbranched core of the HBDLPs was readily functionalized with disulfide bonds, either in the backbone or in the pendant groups. Under reductive conditions, selective cleavage of the disulfides thereby enabled either significant molecular weight reduction, or allowed for triggered release of a covalently bound dye, mimicking a drug. Potentially, such HBDLPs could be stable during circulation, while allowing for selective degradation and/or therapeutic release upon delivery to a cancer tissue.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2015. 69 p.
TRITA-CHE-Report, ISSN 1654-1081 ; 2015:32
National Category
Polymer Technologies
Research subject
Chemical Engineering
urn:nbn:se:kth:diva-173242 (URN)978-91-7595-630-5 (ISBN)
Public defence
2015-10-02, F3, Lindstedtsvägen 26, KTH, Stockholm, 09:00 (English)
Swedish Research Council

QC 20150909

Available from: 2015-09-09 Created: 2015-09-08 Last updated: 2015-09-09Bibliographically approved

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