N-(2-hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging

0490803 - ÚMCH 2019 RIV NL eng J - Článek v odborném periodiku
Fang, J. - Šubr, Vladimír - Islam, W. - Hackbarth, S. - Islam, R. - Etrych, Tomáš - Ulbrich, Karel - Maeda, H.
N-(2-hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging.
European Journal of Pharmaceutics and Biopharmaceutics. Roč. 130, September (2018), s. 165-176. ISSN 0939-6411. E-ISSN 1873-3441
Grant CEP: GA MZd(CZ) NV16-28594A
Grant ostatní: AV ČR(CZ) JSPS-16-05
Program: Bilaterální spolupráce
Institucionální podpora: RVO:61389013
Klíčová slova: EPR effect * polymeric micelles * macromolecular photosensitizers
Obor OECD: Pharmacology and pharmacy
Impakt faktor: 4.708, rok: 2018

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.
Trvalý link: http://hdl.handle.net/11104/0285123