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Biodegradable polymeric vesicles containing magnetic nanoparticles, quantum dots and anticancer drugs for drug delivery and imaging
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2014 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 12, 3885-3894 p.Article in journal (Refereed) Published
Abstract [en]

We have developed biodegradable polymeric vesicles as a nanocarrier system for multimodal bioimaging and anticancer drug delivery. The poly(lactic-co-glycolic acid) (PLGA) vesicles were fabricated by encapsulating inorganic imaging agents of superparamagnetic iron oxide nanoparticles (SPION), manganese-doped zinc sulfide (Mn:ZnS) quantum dots (QDs) and the anticancer drug busulfan into PLGA nanoparticles via an emulsion-evaporation method. T-2(*)-weighted magnetic resonance imaging (MRI) of PLGA-SPION-Mn:ZnS phantoms exhibited enhanced negative contrast with r(2)(*) relaxivity of approximately 523 s(-1) mM(-1) Fe. Murine macrophage (J774A) cellular uptake of PLGA vesicles started fluorescence imaging at 2 h and reached maximum intensity at 24 h incubation. The drug delivery ability of PLGA vesicles was demonstrated in vitro by release of busulfan. PLGA vesicle degradation was studied in vitro, showing that approximately 32% was degraded into lactic and glycolic acid over a period of 5 weeks. The biodistribution of PLGA vesicles was investigated in vivo by MRI in a rat model. Change of contrast in the liver could be visualized by MRI after 7 min and maximal signal loss detected after 4 h post-injection of PLGA vesicles. Histological studies showed that the presence of PLGA vesicles in organs was shifted from the lungs to the liver and spleen over time.

Place, publisher, year, edition, pages
2014. Vol. 35, no 12, 3885-3894 p.
Keyword [en]
Biodegradable polymer, Multifunctional nanoparticles, Anticancer drug delivery, Busulfan, Fluorescence imaging, Magnetic resonance imaging
National Category
Biomaterials Science
URN: urn:nbn:se:kth:diva-144352DOI: 10.1016/j.biomaterials.2014.01.041ISI: 000332431700017ScopusID: 2-s2.0-84893816633OAI: diva2:713442
Swedish Cancer Society

QC 20140423

Available from: 2014-04-23 Created: 2014-04-22 Last updated: 2016-05-16Bibliographically approved
In thesis
1. Synthesis of Polymeric Nanocomposites for Drug Delivery and Bioimaging
Open this publication in new window or tab >>Synthesis of Polymeric Nanocomposites for Drug Delivery and Bioimaging
2016 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Nanomaterials have gained great attention for biomedical applications due to their extraordinary physico-chemical and biological properties. The current dissertation presents the design and development of multifunctional nanoparticles for molecular imaging and controlled drug delivery applications which include biodegradable polymeric nanoparticles, superparamagnetic iron oxide nanoparticles (SPION)/polymeric nanocomposite for magnetic resonance imaging (MRI) and drug delivery, manganese-doped zinc sulfide (Mn:ZnS) quantum dots (QDs)/ SPION/ polymeric nanocomposites for fluorescence imaging, MRI and drug delivery.Bioimaging is an important function of multifunctional nanoparticles in this thesis. Imaging probes were made of SPION and Mn:ZnS QDs for in vitro and in vivo imaging. The SPION have been prepared through a high temperature decomposition method to be used as MRI contrast agent. SPION and Mn:ZnS were encapsulated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles during the particles formation. The hydrophobic model drug, busulphan, was loaded in the PLGA vesicles in the composite particles. T2*-weighted MRI of SPION-Mn:ZnS-PLGA phantoms exhibited enhanced negative contrast with r2* relaxivity of 523 mM-1 s-1. SPION-Mn:ZnS-PLGA-NPs have been successfully applied to enhance the contrast of liver in rat model.The biodegradable and biocompatible poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) was used as matrix materials for polymeric nanoparticles -based drug delivery system. The PEG-PCL nanoparticles have been constructed to encapsulate SPION and therapeutic agent. The encapsulation efficiency of busulphan was found to be ~ 83 %. PEG-PCL nanoparticles showed a sustained release of the loaded busulphan over a period of 10 h. The SPION-PEG-PCL phantoms showed contrast enhancement in T2*-weighted MRI. Fluorescein-labeled PEG-PCL nanoparticles have been observed in the cytoplasm of the murine macrophage cells (J774A) by fluorescence microscopy. Around 100 % cell viability were noticed for PEG-PCL nanoparticles when incubated with HL60 cell line. The in vivo biodistribution of fluorescent tagged PEG-PCL nanoparticles demonstrated accumulation of PEG-PCL nanoparticles in different tissues including lungs, spleen, liver and kidneys after intravenous administration.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2016. 42 p.
Biodegradable polymers, SPION, QDs, drug delivery, cytotoxicity, MRI, in vivo fluorescence imaging, biodistribution
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
urn:nbn:se:kth:diva-186300 (URN)978-91-7595-930-6 (ISBN)
2016-06-10, Sal C, Isafjordsgatan 26, Kista, Stockholm, 10:00 (English)

QC 20160516

Available from: 2016-05-16 Created: 2016-05-09 Last updated: 2016-05-17Bibliographically approved

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