PMID- 28697952
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20240314
IS  - 1872-8294 (Electronic)
IS  - 0169-409X (Print)
IS  - 0169-409X (Linking)
VI  - 119
DP  - 2017 Sep 15
TI  - Pharmacological and physical vessel modulation strategies to improve EPR-mediated 
      drug targeting to tumors.
PG  - 44-60
LID - S0169-409X(17)30104-7 [pii]
LID - 10.1016/j.addr.2017.07.007 [doi]
AB  - The performance of nanomedicine formulations depends on the Enhanced Permeability 
      and Retention (EPR) effect. Prototypic nanomedicine-based drug delivery systems, 
      such as liposomes, polymers and micelles, aim to exploit the EPR effect to 
      accumulate at pathological sites, to thereby improve the balance between drug 
      efficacy and toxicity. Thus far, however, tumor-targeted nanomedicines have not 
      yet managed to achieve convincing therapeutic results, at least not in large 
      cohorts of patients. This is likely mostly due to high inter- and intra-patient 
      heterogeneity in EPR. Besides developing (imaging) biomarkers to monitor and 
      predict EPR, another strategy to address this heterogeneity is the establishment 
      of vessel modulation strategies to homogenize and improve EPR. Over the years, 
      several pharmacological and physical co-treatments have been evaluated to improve 
      EPR-mediated tumor targeting. These include pharmacological strategies, such as 
      vessel permeabilization, normalization, disruption and promotion, as well as 
      physical EPR enhancement via hyperthermia, radiotherapy, sonoporation and 
      phototherapy. In the present manuscript, we summarize exemplary studies showing 
      that pharmacological and physical vessel modulation strategies can be used to 
      improve tumor-targeted drug delivery, and we discuss how these advanced 
      combination regimens can be optimally employed to enhance the (pre-) clinical 
      performance of tumor-targeted nanomedicines.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Ojha, Tarun
AU  - Ojha T
AD  - Department of Nanomedicines and Theranostics, Institute for Experimental 
      Molecular Imaging (ExMI), RWTH Aachen University Clinic, 52074 Aachen, Germany; 
      Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences 
      (UIPS), Utrecht University, 3584 CG, Utrecht, The Netherlands.
FAU - Pathak, Vertika
AU  - Pathak V
AD  - Department of Nanomedicines and Theranostics, Institute for Experimental 
      Molecular Imaging (ExMI), RWTH Aachen University Clinic, 52074 Aachen, Germany.
FAU - Shi, Yang
AU  - Shi Y
AD  - Department of Nanomedicines and Theranostics, Institute for Experimental 
      Molecular Imaging (ExMI), RWTH Aachen University Clinic, 52074 Aachen, Germany.
FAU - Hennink, Wim E
AU  - Hennink WE
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences 
      (UIPS), Utrecht University, 3584 CG, Utrecht, The Netherlands.
FAU - Moonen, Chrit T W
AU  - Moonen CTW
AD  - Imaging division, University Medical Center Utrecht (UMCU), Utrecht, The 
      Netherlands.
FAU - Storm, Gert
AU  - Storm G
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences 
      (UIPS), Utrecht University, 3584 CG, Utrecht, The Netherlands; Department of 
      Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical 
      Medicine, University of Twente, 7500 AE Enschede, The Netherlands.
FAU - Kiessling, Fabian
AU  - Kiessling F
AD  - Department of Nanomedicines and Theranostics, Institute for Experimental 
      Molecular Imaging (ExMI), RWTH Aachen University Clinic, 52074 Aachen, Germany. 
      Electronic address: fkiessling@ukaachen.de.
FAU - Lammers, Twan
AU  - Lammers T
AD  - Department of Nanomedicines and Theranostics, Institute for Experimental 
      Molecular Imaging (ExMI), RWTH Aachen University Clinic, 52074 Aachen, Germany; 
      Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences 
      (UIPS), Utrecht University, 3584 CG, Utrecht, The Netherlands; Department of 
      Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical 
      Medicine, University of Twente, 7500 AE Enschede, The Netherlands. Electronic 
      address: tlammers@ukaachen.de.
LA  - eng
GR  - 309495/ERC_/European Research Council/International
GR  - 680882/ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170708
PL  - Netherlands
TA  - Adv Drug Deliv Rev
JT  - Advanced drug delivery reviews
JID - 8710523
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*administration & dosage/chemistry
MH  - Drug Delivery Systems/methods
MH  - Humans
MH  - Nanomedicine/methods
MH  - Neoplasms/*drug therapy
MH  - Permeability/*drug effects
PMC - PMC5919100
MID - EMS77387
OTO - NOTNLM
OT  - Disruption
OT  - Drug delivery
OT  - EPR
OT  - Hyperthermia
OT  - Nanomedicine
OT  - Normalization
OT  - Permeabilization
OT  - Phototherapy
OT  - Promotion
OT  - Radiotherapy
OT  - Sonoporation
OT  - Tumor targeting
EDAT- 2017/07/13 06:00
MHDA- 2018/07/10 06:00
PMCR- 2018/04/26
CRDT- 2017/07/13 06:00
PHST- 2017/04/01 00:00 [received]
PHST- 2017/06/22 00:00 [revised]
PHST- 2017/07/06 00:00 [accepted]
PHST- 2017/07/13 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2017/07/13 06:00 [entrez]
PHST- 2018/04/26 00:00 [pmc-release]
AID - S0169-409X(17)30104-7 [pii]
AID - 10.1016/j.addr.2017.07.007 [doi]
PST - ppublish
SO  - Adv Drug Deliv Rev. 2017 Sep 15;119:44-60. doi: 10.1016/j.addr.2017.07.007. Epub 
      2017 Jul 8.