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N-(2-hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging
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SYSNO ASEP 0490803 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title N-(2-hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging Author(s) Fang, J. (JP)
Šubr, Vladimír (UMCH-V) RID, ORCID
Islam, W. (JP)
Hackbarth, S. (DE)
Islam, R. (JP)
Etrych, Tomáš (UMCH-V) RID, ORCID
Ulbrich, Karel (UMCH-V) RID
Maeda, H. (JP)Source Title European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier - ISSN 0939-6411
Roč. 130, September (2018), s. 165-176Number of pages 12 s. Language eng - English Country NL - Netherlands Keywords EPR effect ; polymeric micelles ; macromolecular photosensitizers Subject RIV FR - Pharmacology ; Medidal Chemistry OECD category Pharmacology and pharmacy R&D Projects NV16-28594A GA MZd - Ministry of Health (MZ) Institutional support UMCH-V - RVO:61389013 UT WOS 000441855500018 EID SCOPUS 85049321770 DOI 10.1016/j.ejpb.2018.06.005 Annotation Tumor-targeted photodynamic therapy (PDT) using polymeric photosensitizers is a promising therapeutic strategy for cancer treatment. In this study, we synthesized a pHPMA conjugated pyropheophorbide-a (P-PyF) as a cancer theranostic agent for PDT and photodynamic diagnostics (PDD). Pyropheophorbide-a has one carboxyl group which was conjugated to pHPMA via amide bond yielding the intended product with high purity. In aqueous solutions, P-PyF showed a mean particle size of approximately 200 nm as it forms micelle which exhibited fluorescence quenching and thus very little singlet oxygen (1O2) production. In contrast, upon disruption of micelle strong fluorescence and 1O2 production were observed. In vitro study clearly showed the PDT effect of P-PyF. More potent 1O2 production and PDT effect were observed during irradiation at approximately 420 nm, the maximal absorbance of pyropheophorbide-a, than irradiation at longer wavelength (i.e., approximately 680 nm), suggesting selection of proper absorption light is essential for successful PDT. In vivo study showed high tumor accumulation of P-PyF compared with most of normal tissues due to the enhanced permeability and retention (EPR) effect, which resulting in superior antitumor effect under irradiation using normal xenon light source of endoscope, and clear tumor imaging profiles even in the metastatic lung cancer at 28 days after administration of P-PyF. On the contrary irradiation using long wavelength (i.e., approximately 680 nm), the lowest Q-Band, exhibited remarkable tumor imaging effect with little autofluorescence of background. These findings strongly suggested P-PyF may be a potential candidate-drug for PDT/PDD, particularly using two different wavelength for treatment and detection/imaging, respectively. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2019
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