The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect

2011 ◽  
Vol 63 (3) ◽  
pp. 136-151 ◽  
Author(s):  
Jun Fang ◽  
Hideaki Nakamura ◽  
Hiroshi Maeda
Keyword(s):  
Drug Delivery ◽  
Blood Vessels ◽  
Epr Effect ◽  
Tumor Blood Vessels

scholarly journals Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

2021 ◽  
Vol 11 (2) ◽  
pp. 124
Author(s):  
Dong Huang ◽  
Lingna Sun ◽  
Leaf Huang ◽  
Yanzuo Chen
Keyword(s):  
Blood Vessels ◽  
Tumor Vessels ◽  
Epr Effect ◽  
Nanodrug Delivery ◽  
Enhanced Permeability And Retention ◽  
Macromolecular Drugs ◽  
Long Time ◽  
Vessel Network ◽  
Tumor Blood Vessels ◽  
The Relationship

The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, a disordered vessel network, and occluded or embolized tumor blood vessels seriously limit the EPR effect. To augment the EPR effect and improve curative effects, in this review, we focused on the perspective of tumor blood vessels, and analyzed the relationship among abnormal angiogenesis, abnormal vascular structure, irregular blood flow, extensive permeability of tumor vessels, and the EPR effect. In this commentary, nanoparticles including liposomes, micelles, and polymers extravasate through the tumor vasculature, which are based on modulating tumor vessels, to increase the EPR effect, thereby increasing their therapeutic effect.

scholarly journals Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sijumon Kunjachan ◽  
Shady Kotb ◽  
Robert Pola ◽  
Michal Pechar ◽  
Rajiv Kumar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Vessels ◽  
Fold Increase ◽  
Effective Drug ◽  
Human Pancreatic Cancer ◽  
Standard Drug ◽  
Fluorescence Studies ◽  
Nanodrug Delivery ◽  
Functional Changes ◽  
Tumor Blood Vessels

Abstract Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the tumor vascular barrier in a human pancreatic cancer model. Clinical radiation activates the tumor endothelial-targeted gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these tumor neovessels lead to distinct changes in tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared dye, demonstrate more than two-fold increase in nanodrug delivery, post tumor vascular modulation. Functional changes in altered tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted therapy effectively invades the tumor vascular barrier and improve nanodrug delivery in a human pancreatic tumor model and it may also be applied to other nonresectable, intransigent tumors that barely respond to standard drug therapies.

Peptide-guided drug delivery to radiation-induced targets in tumor blood vessels

2003 ◽  
Vol 57 (2) ◽  
pp. S317-S318
Author(s):  
A Cmelak ◽  
B Chak ◽  
C Scarfone ◽  
W Martin ◽  
D Hallahan
Keyword(s):  
Drug Delivery ◽  
Blood Vessels ◽  
Radiation Induced ◽  
Tumor Blood Vessels

Radiation-guided drug delivery to tumor blood vessels results in improved tumor growth delay

2004 ◽  
Vol 99 (3) ◽  
pp. 369-381 ◽  
Author(s):  
Ling Geng ◽  
Katherine Osusky ◽  
Sekhar Konjeti ◽  
Allie Fu ◽  
Dennis Hallahan
Keyword(s):  
Drug Delivery ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Growth Delay ◽  
Tumor Growth Delay ◽  
Tumor Blood Vessels

scholarly journals Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Han-Chung Wu ◽  
De-Kuan Chang
Keyword(s):  
Drug Delivery ◽  
Endothelial Cells ◽  
Blood Vessels ◽  
Antiangiogenic Therapy ◽  
Anticancer Therapy ◽  
Liposomal Drug ◽  
Surface Receptors ◽  
Low Toxicity ◽  
Tumor Blood Vessels ◽  
Potential Methods

Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

scholarly journals Peptide-Mediated Targeting to Tumor Blood Vessels of Lung Cancer for Drug Delivery

2007 ◽  
Vol 67 (22) ◽  
pp. 10958-10965 ◽  
Author(s):  
Tong-Young Lee ◽  
Chin-Tarng Lin ◽  
Szu-Yao Kuo ◽  
De-Kuan Chang ◽  
Han-Chung Wu
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Blood Vessels ◽  
Tumor Blood Vessels

Targeted drug delivery of Sunitinib Malate to tumor blood vessels by cRGD-chiotosan-gold nanoparticles

2017 ◽  
Vol 517 (1-2) ◽  
pp. 269-278 ◽  
Author(s):  
Mohaddeseh Mahmoudi Saber ◽  
Sara Bahrainian ◽  
Rassoul Dinarvand ◽  
Fatemeh Atyabi
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Blood Vessels ◽  
Targeted Drug Delivery ◽  
Sunitinib Malate ◽  
Targeted Drug ◽  
Tumor Blood Vessels

scholarly journals Targeted Drug Delivery by Radiation-Induced Tumor Vascular Modulation

2018 ◽  
Author(s):  
Sijumon Kunjachan ◽  
Shady Kotb ◽  
Rajiv Kumar ◽  
Robert Pola ◽  
Michal Pechar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Vessels ◽  
Targeted Drug Delivery ◽  
Therapeutic Benefit ◽  
Human Pancreatic Cancer ◽  
Nanodrug Delivery ◽  
Functional Changes ◽  
Radiation Induced ◽  
Targeted Drug ◽  
Tumor Blood Vessels

Effective drug delivery is severely restricted by the presence of complex pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, mature and hypopermeable tumor blood vessels limit the permeation and penetration of chemo or nanotherapeutics to cancer cells and substantially reduce the treatment efficacy. New, clinically-viable strategies are therefore sought to breach the neoplastic barriers that prevent optimal tumor-specific drug delivery. Here, we present an original idea to boost targeted drug delivery by selectively knocking down the tumor vascular barrier in a poorly permeable human pancreatic cancer model. For the first time, we demonstrate that clinical irradiation (10 Gy, 6 MV) can induce tumor vascular modulation when combined with tumor endothelial-targeting gold nanoparticles. Active disruption of tumor blood vessels by nanoparticle-combined radiotherapy led to increased vessel permeability and improved tumor uptake of two prototypical model nanodrugs: i) a short-circulating nanocarrier with MR-sensitive gadolinium (Gad-NC; 8 kDa; t1/2=1.5 h) and ii) a long-circulating nanocarrier with fluorescence-sensitive NIR dye (FL-NC; 30 kDa; t1/2=25 h). Functional changes in the altered tumor vessel dynamics, measured by relative changes in permeability (Ktrans), flux rate (Kep) and extracellular interstitial volume (Ve) were consistent with the concomitant increase in nanodrug delivery. This combination of radiation-induced antivascular and nanodrug-mediated anti-tumor treatment offers high therapeutic benefit for tumors with pathophysiology that restricts efficient drug delivery.

scholarly journals Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels

Cancer Cell ◽  
2003 ◽  
Vol 3 (1) ◽  
pp. 63-74 ◽  
Author(s):  
Dennis Hallahan ◽  
Ling Geng ◽  
Shimian Qu ◽  
Christopher Scarfone ◽  
Todd Giorgio ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Vessels ◽  
Tumor Blood Vessels
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