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Development and biodistribution of a theranostic aluminum phthalocyanine nanophotosensitizer
KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM. Karolinska Inst, Sweden.ORCID iD: 0000-0001-8887-9141
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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) PublishedText
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.

Place, publisher, year, edition, pages
2016. Vol. 13, 48-57 p.
Keyword [en]
Aluminum phthalocyanine, Copolymer, Nanoparticles, Nanophotosensitizer, Biodistribution, Imaging
National Category
Cancer and Oncology
URN: urn:nbn:se:kth:diva-185380DOI: 10.1016/j.pdpdt.2015.12.005ISI: 000372376500009PubMedID: 26708297ScopusID: 2-s2.0-84960932016OAI: diva2:920544
Swedish Cancer SocietySwedish Childhood Cancer Foundation

QC 20160418

Available from: 2016-04-18 Created: 2016-04-18 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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