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In Vitro Evaluation of Non-Protein Adsorbing Breast Cancer Theranostics Based on 19F-Polymer Containing Nanoparticles
KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.ORCID iD: 0000-0001-9035-4547
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2013 (English)In: Particle & particle systems characterization, ISSN 0934-0866, E-ISSN 1521-4117, Vol. 30, no 4, 381-390 p.Article in journal (Refereed) Published
Abstract [en]

Eight fluorinated nanoparticles (NPs) are synthesized, loaded with doxorubicin (DOX), and evaluated as theranostic delivery platforms to breast cancer cells. The multifunctional NPs are formed by self-assembly of either linear or star-shaped amphiphilic block copolymers, with fluorinated segments incorporated in the hydrophilic corona of the carrier. The sizes of the NPs confirm that small circular NPs are formed. The release kinetics data of the particles reveals clear hydrophobic core dependence, with longer sustained release from particles with larger hydrophobic cores, suggesting that the DOX release from these carriers can be tailored. Viability assays and flow cytometry evaluation of the ratios of apoptosis/necrosis indicate that the materials are non-toxic to breast cancer cells before DOX loading; however, they are very efficient, similar to free DOX, at killing cancer cells after drug encapsulation. Both flow cytometry and confocal microscopy confirm the cellular uptake of NPs and DOX-NPs into breast cancer cells, and in vitro 19F-MRI measurement shows that the fluorinated NPs have strong imaging signals, qualifying them as a potential in vivo contrast agent for 19F-MRI.

Place, publisher, year, edition, pages
2013. Vol. 30, no 4, 381-390 p.
Keyword [en]
polymers, theranostic nanoparticles, drug delivery, doxorubicin, breast cancer
National Category
Other Chemistry Topics
URN: urn:nbn:se:kth:diva-123125DOI: 10.1002/ppsc.201300018ISI: 000318106000012ScopusID: 2-s2.0-84876724571OAI: diva2:625147
Swedish Research Council, 2011-3720 2009-3259Vinnova

QC 20130604

Available from: 2013-06-04 Created: 2013-06-03 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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Porsch, ChristianMalmström, Eva
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