PMID- 29885851
OWN - NLM
STAT- MEDLINE
DCOM- 20181105
LR  - 20181105
IS  - 1873-3441 (Electronic)
IS  - 0939-6411 (Linking)
VI  - 130
DP  - 2018 Sep
TI  - N-(2-hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a 
      promising tumor-targeted theranostic probe for photodynamic therapy and imaging.
PG  - 165-176
LID - S0939-6411(18)30493-4 [pii]
LID - 10.1016/j.ejpb.2018.06.005 [doi]
AB  - 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 ((1)O(2)) production. In contrast, upon disruption of 
      micelle strong fluorescence and (1)O(2) production were observed. In vitro study 
      clearly showed the PDT effect of P-PyF. More potent (1)O(2) 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.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Fang, Jun
AU  - Fang J
AD  - Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo 
      University, Kumamoto 860-0082, Japan. Electronic address: 
      fangjun@ph.sojo-u.ac.jp.
FAU - Subr, Vladimir
AU  - Subr V
AD  - Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq. 
      2, 16206 Prague 6, Czech Republic.
FAU - Islam, Waliul
AU  - Islam W
AD  - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 
      University, Kumamoto 860-8556, Japan.
FAU - Hackbarth, Steffen
AU  - Hackbarth S
AD  - Institute of Physics, Photobiophysics, Humboldt University of Berlin, Newtonstr. 
      15, 12489 Berlin, Germany.
FAU - Islam, Rayhanul
AU  - Islam R
AD  - Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo 
      University, Kumamoto 860-0082, Japan.
FAU - Etrych, Tomas
AU  - Etrych T
AD  - Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq. 
      2, 16206 Prague 6, Czech Republic.
FAU - Ulbrich, Karel
AU  - Ulbrich K
AD  - Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq. 
      2, 16206 Prague 6, Czech Republic.
FAU - Maeda, Hiroshi
AU  - Maeda H
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20180608
PL  - Netherlands
TA  - Eur J Pharm Biopharm
JT  - European journal of pharmaceutics and biopharmaceutics : official journal of 
      Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
JID - 9109778
RN  - 0 (Micelles)
RN  - 0 (Photosensitizing Agents)
RN  - 0 (Polymers)
RN  - 0 (Polymethacrylic Acids)
RN  - 1406-65-1 (Chlorophyll)
RN  - 24533-72-0 (pyropheophorbide a)
RN  - 40704-75-4 (Duxon)
SB  - IM
MH  - Animals
MH  - Chlorophyll/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Fluorescence
MH  - Lung Neoplasms/diagnosis/*drug therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Micelles
MH  - Particle Size
MH  - Permeability
MH  - Photochemotherapy/*methods
MH  - Photosensitizing Agents/administration & dosage
MH  - Polymers/chemistry
MH  - Polymethacrylic Acids/*chemistry
MH  - Theranostic Nanomedicine/methods
MH  - Time Factors
MH  - Tissue Distribution
OTO - NOTNLM
OT  - EPR effect
OT  - Macromolecular photosensitizers
OT  - Polymeric micelles
OT  - Pyropheoporbide-a
OT  - Singlet oxygen
OT  - Tumor targeting
EDAT- 2018/06/11 06:00
MHDA- 2018/11/06 06:00
CRDT- 2018/06/11 06:00
PHST- 2018/04/17 00:00 [received]
PHST- 2018/06/06 00:00 [revised]
PHST- 2018/06/06 00:00 [accepted]
PHST- 2018/06/11 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2018/06/11 06:00 [entrez]
AID - S0939-6411(18)30493-4 [pii]
AID - 10.1016/j.ejpb.2018.06.005 [doi]
PST - ppublish
SO  - Eur J Pharm Biopharm. 2018 Sep;130:165-176. doi: 10.1016/j.ejpb.2018.06.005. Epub 
      2018 Jun 8.