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Synthesis of Polymeric Nanocomposites for Drug Delivery and Bioimaging
KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM.ORCID iD: 0000-0001-8887-9141
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.
Keyword [en]
Biodegradable polymers, SPION, QDs, drug delivery, cytotoxicity, MRI, in vivo fluorescence imaging, biodistribution
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
Physics
Identifiers
URN: urn:nbn:se:kth:diva-186300ISBN: 978-91-7595-930-6 (print)OAI: oai:DiVA.org:kth-186300DiVA: diva2:927411
Presentation
2016-06-10, Sal C, Isafjordsgatan 26, Kista, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20160516

Available from: 2016-05-16 Created: 2016-05-09 Last updated: 2016-05-17Bibliographically approved
List of papers
1. Biodegradable polymeric vesicles containing magnetic nanoparticles, quantum dots and anticancer drugs for drug delivery and imaging
Open this publication in new window or tab >>Biodegradable polymeric vesicles containing magnetic nanoparticles, quantum dots and anticancer drugs for drug delivery and imaging
Show others...
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.

Keyword
Biodegradable polymer, Multifunctional nanoparticles, Anticancer drug delivery, Busulfan, Fluorescence imaging, Magnetic resonance imaging
National Category
Biomaterials Science
Identifiers
urn:nbn:se:kth:diva-144352 (URN)10.1016/j.biomaterials.2014.01.041 (DOI)000332431700017 ()2-s2.0-84893816633 (Scopus ID)
Funder
Swedish Cancer Society
Note

QC 20140423

Available from: 2014-04-23 Created: 2014-04-22 Last updated: 2017-12-05Bibliographically approved
2. Development and biodistribution of a theranostic aluminum phthalocyanine nanophotosensitizer
Open this publication in new window or tab >>Development and biodistribution of a theranostic aluminum phthalocyanine nanophotosensitizer
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2016 (English)In: Photodiagnosis and Photodynamic Therapy, ISSN 1572-1000, E-ISSN 1873-1597, Vol. 13, 48-57 p.Article in journal (Refereed) Published
Abstract [en]

Background: Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS) with high fluorescence ability. Its use in photodynamic therapy (PDT) is hampered by hydrophobicity and poor biodistribution. Methods: AlPc was converted to a biocompatible nanostructure by incorporation into amphiphilic polyethylene glycol-polycaprolactone (PECL) copolymer nanoparticles, allowing efficient entrapment of the PS in the hydrophobic core, water dispersibility and biodistribution enhancement by PEG-induced surface characteristics. A series of synthesized PECL copolymers were used to prepare nanophotosensitizers with an average diameter of 66.5-99.1 nm and encapsulation efficiency (EE%) of 66.4-78.0%. One formulation with favorable colloidal properties and relatively slow release over 7 days was selected for in vitro photophysical assessment and in vivo biodistribution studies in mice. Results: The photophysical properties of AlPc were improved by encapsulating AlPc into PECL-NPs, which showed intense fluorescence emission at 687 nm and no AlPc aggregation has been induced after entrapment into the nanoparticles. Biodistribution of AlPc loaded NPs (AlPc-NPs) and free AlPc drug in mice was monitored by in vivo whole body fluorescence imaging and ex vivo organ imaging, with in vivo imaging system (IVIS). Compared to a AlPc solution in aqueous TWEEN 80 (2 w/v%), the developed nanophotosensitizer showed targeted drug delivery to lungs, liver and spleen as monitored by the intrinsic fluorescence of AlPc at different time points (1 h, 24 h and 48 h) post iv. administration. Conclusions: The AlPc-based copolymer nanoparticles developed offer potential as a single agent multifunctional theranostic nanophotosensitizer for PDT coupled with imaging-guided drug delivery and biodistribution, and possibly also fluorescence diagnostics.

Keyword
Aluminum phthalocyanine, Copolymer, Nanoparticles, Nanophotosensitizer, Biodistribution, Imaging
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:kth:diva-185380 (URN)10.1016/j.pdpdt.2015.12.005 (DOI)000372376500009 ()26708297 (PubMedID)2-s2.0-84960932016 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Childhood Cancer Foundation
Note

QC 20160418

Available from: 2016-04-18 Created: 2016-04-18 Last updated: 2017-11-30Bibliographically approved
3. Biodistribution of Busulphan Loaded Biodegradable Nano-carrier Designed for Multimodal Imaging
Open this publication in new window or tab >>Biodistribution of Busulphan Loaded Biodegradable Nano-carrier Designed for Multimodal Imaging
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Multifunctional nanocarriers for pathological site imaging and regulated drug delivery are increasingly promising for disease diagnosis and treatment. We developed a multifunctional theranostic nanocarrier system for anticancer drug delivery and molecular imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent and busulphan as an antineoplastic agent were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) nanoparticles (NPs) via the emulsion-evaporation method. Busulphan entrapment efficiency was 83% and the drug release showed a sustained pattern over 10 hours. SPION loaded-PEG-PCL NPs showed contrast enhancement in T2*-weighted MRI with high r2* relaxivity. In vitro time-dependent cellular PEG-PCL NP uptake was observed in macrophage cells (J774A). PEG-PCL NPs were further functionalized with VivoTag 680XL Fluorochrome for in vivo fluorescence imaging for study of their biodistribution in Balb/c mice over 48 h. The results of real-time imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL NPs were highly distributed in the lungs until 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h. No pathological impairment was found in the studied tissues. Thus, PEG-PCL NPs as biodegradable and biocompatible nanocarriers are an efficient multimodal imaging agent, offer high drug loading capacity, and provide the possibility of disease treatment.

Keyword
Biodegradable polymer, drug delivery, magnetic resonance imaging, cellular uptake, cytotoxicity, biodistribution, in vivo fluorescence imaging, fluorescence/CT imaging co- registration
National Category
Physical Sciences
Research subject
Chemistry
Identifiers
urn:nbn:se:kth:diva-187049 (URN)
Note

QC 20160518

Available from: 2016-05-16 Created: 2016-05-16 Last updated: 2016-05-18Bibliographically approved

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