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N-(2-hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging
J. Fang, V. Šubr, W. Islam, S. Hackbarth, R. Islam, T. Etrych, K. Ulbrich, H. Maeda,
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články
Grantová podpora
NV16-28594A
MZ0
CEP - Centrální evidence projektů
- MeSH
- časové faktory MeSH
- chlorofyl aplikace a dávkování analogy a deriváty farmakokinetika MeSH
- fluorescence MeSH
- fotochemoterapie metody MeSH
- fotosenzibilizující látky aplikace a dávkování MeSH
- kyseliny polymethakrylové chemie MeSH
- micely MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádory plic diagnóza farmakoterapie MeSH
- permeabilita MeSH
- polymery chemie MeSH
- teranostická nanomedicína metody MeSH
- tkáňová distribuce MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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 ∼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 ∼420 nm, the maximal absorbance of pyropheophorbide-a, than irradiation at longer wavelength (i.e., ∼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., ∼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.
BioDynamics Research Foundation Kumamoto 862 0954 Japan
Institute of Physics Photobiophysics Humboldt University of Berlin Newtonstr 15 12489 Berlin Germany
Osaka University Graduate School of Medicine Suita Osaka Japan
Citace poskytuje Crossref.org
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- $a Fang, Jun $u Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan. Electronic address: fangjun@ph.sojo-u.ac.jp.
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- $a N-(2-hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging / $c J. Fang, V. Šubr, W. Islam, S. Hackbarth, R. Islam, T. Etrych, K. Ulbrich, H. Maeda,
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- $a 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 ∼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 ∼420 nm, the maximal absorbance of pyropheophorbide-a, than irradiation at longer wavelength (i.e., ∼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., ∼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.
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- $a Šubr, Vladimír $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq. 2, 16206 Prague 6, Czech Republic.
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- $a Islam, Waliul $u Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
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- $a Maeda, Hiroshi $u Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan; BioDynamics Research Foundation, Kumamoto 862-0954, Japan; Osaka University, Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: maedabdr@sweet.ocn.ne.jp.
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