PMID- 26237291
OWN - NLM
STAT- MEDLINE
DCOM- 20161219
LR  - 20220330
IS  - 1549-8719 (Electronic)
IS  - 1073-9688 (Linking)
VI  - 23
IP  - 3
DP  - 2016 Apr
TI  - A Retrospective 30 Years After Discovery of the Enhanced Permeability and 
      Retention Effect of Solid Tumors: Next-Generation Chemotherapeutics and 
      Photodynamic Therapy--Problems, Solutions, and Prospects.
PG  - 173-82
LID - 10.1111/micc.12228 [doi]
AB  - Solid tumor has unique vascular architecture, excessive production of vascular 
      mediators, and extravasation of macromolecules from blood vessels into the tumor 
      tissue interstitium. These features comprise the phenomenon named the EPR effect 
      of solid tumors, described in 1986. Our investigations on the EPR revealed that 
      many mediators, such as bradykinin, NO, and prostaglandins, are involved in the 
      EPR effect, which is now believed to be the most important element for 
      cancer-selective drug delivery. However, tumors in vivo manifest great diversity, 
      and some demonstrate a poor EPR effect, for example, because of impaired vascular 
      flow involving thrombosis, with poor drug delivery and therapeutic failure. 
      Another important element of this effect is that it operates in metastatic 
      cancers. Because few drugs are currently effective against metastases, the EPR 
      effect offers a great advantage in nanomedicine therapy. The EPR effect can also 
      be augmented two to three times via nitroglycerin, ACE inhibitors, and 
      angiotensin II-induced hypertension. The delivery of nanomedicines to tumors can 
      thereby be enhanced. In traditional PDT, most PSs had low MW and little 
      tumor-selective accumulation. Our 
      hydroxypropylmetacrylamide-polymer-conjugated-PS, zinc protoporphyrin (apparent 
      MW >50 kDa) showed tumor-selective accumulation, as revealed by fluorescent 
      imaging of autochthonous cancers. After one i.v. injection of polymeric PS 
      followed by two or three xenon light irradiation/treatments, most tumors 
      regressed. Thus, nanoprobes with the EPR effect seem to have remarkable effects. 
      Enhancing the EPR effect by using vascular modulators will aid innovations in PDT 
      for greater tumor-targeted drug delivery.
CI  - (c) 2015 John Wiley & Sons Ltd.
FAU - Maeda, Hiroshi
AU  - Maeda H
AD  - Institute of Drug Delivery Science, Sojo University, Kumamoto, Japan.
FAU - Tsukigawa, Kenji
AU  - Tsukigawa K
AD  - Institute of Drug Delivery Science, Sojo University, Kumamoto, Japan.
FAU - Fang, Jun
AU  - Fang J
AD  - Institute of Drug Delivery Science, Sojo University, Kumamoto, Japan.
LA  - eng
PT  - Historical Article
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Microcirculation
JT  - Microcirculation (New York, N.Y. : 1994)
JID - 9434935
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Antineoplastic Agents/history/*therapeutic use
MH  - Drug Delivery Systems/history/*methods
MH  - History, 20th Century
MH  - History, 21st Century
MH  - Neoplasm Metastasis
MH  - *Neoplasms/blood/pathology/therapy
MH  - *Neovascularization, Pathologic/metabolism/pathology/therapy
MH  - Permeability
MH  - Photochemotherapy/history/*methods
OTO - NOTNLM
OT  - anticancer therapy
OT  - enhanced permeability and retention effect
OT  - nanomedicine
OT  - photodynamic therapy
EDAT- 2015/08/04 06:00
MHDA- 2016/12/20 06:00
CRDT- 2015/08/04 06:00
PHST- 2015/06/19 00:00 [received]
PHST- 2015/07/29 00:00 [accepted]
PHST- 2015/08/04 06:00 [entrez]
PHST- 2015/08/04 06:00 [pubmed]
PHST- 2016/12/20 06:00 [medline]
AID - 10.1111/micc.12228 [doi]
PST - ppublish
SO  - Microcirculation. 2016 Apr;23(3):173-82. doi: 10.1111/micc.12228.