Next Article in Journal
In Vitro–In Vivo Correlations Based on In Vitro Dissolution of Parent Drug Diltiazem and Pharmacokinetics of Its Metabolite
Next Article in Special Issue
Hydroxyurea-Loaded Albumin Nanoparticles: Preparation, Characterization, and In Vitro Studies
Previous Article in Journal
Influenza Virus-Like Particles Presenting both Toxoplasma gondii ROP4 and ROP13 Enhance Protection against T. gondii Infection
Previous Article in Special Issue
Paclitaxel Magnetic Core–Shell Nanoparticles Based on Poly(lactic acid) Semitelechelic Novel Block Copolymers for Combined Hyperthermia and Chemotherapy Treatment of Cancer
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle

Augmentation of EPR Effect and Efficacy of Anticancer Nanomedicine by Carbon Monoxide Generating Agents

1
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan
2
Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
3
Biodynamics Research Foundation, Kumamoto 862-0954, Japan
4
Department of General Surgery, Sheng Jing Hospital, China Medical University, Shenyang 110011, China
5
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague 16206, Czech Republic
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this paper.
Pharmaceutics 2019, 11(7), 343; https://doi.org/10.3390/pharmaceutics11070343
Received: 14 June 2019 / Revised: 11 July 2019 / Accepted: 12 July 2019 / Published: 16 July 2019
(This article belongs to the Special Issue Advanced Polymeric Delivery Systems for Cancer Therapy)
  |  
PDF [6252 KB, uploaded 16 July 2019]
  |     |  

Abstract

One obstacle to the successful delivery of nanodrugs into solid tumors is the heterogeneity of an enhanced permeability and retention (EPR) effect as a result of occluded or embolized tumor blood vessels. Therefore, the augmentation of the EPR effect is critical for satisfactory anticancer nanomedicine. In this study, we focused on one vascular mediator involved in the EPR effect, carbon monoxide (CO), and utilized two CO generating agents, one is an extrinsic CO donor (SMA/CORM2 micelle) and another is an inducer of endogenous CO generation via heme oxygenase-1 (HO-1) induction that is carried out using pegylated hemin. Both agents generated CO selectively in solid tumors, which resulted in an enhanced EPR effect and a two- to three-folds increased tumor accumulation of nanodrugs. An increase in drug accumulation in the normal tissue did not occur with the treatment of CO generators. In vivo imaging also clearly indicated a more intensified fluorescence of macromolecular nanoprobe in solid tumors when combined with these CO generators. Consequently, the combination of CO generators with anticancer nanodrugs resulted in an increased anticancer effect in the different transplanted solid tumor models. These findings strongly warrant the potential application of these CO generators as EPR enhancers in order to enhance tumor detection and therapy using nanodrugs. View Full-Text
Keywords: EPR effect; nanomedicine; carbon monoxide; PDT; nanoprobe EPR effect; nanomedicine; carbon monoxide; PDT; nanoprobe
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Fang, J.; Islam, R.; Islam, W.; Yin, H.; Subr, V.; Etrych, T.; Ulbrich, K.; Maeda, H. Augmentation of EPR Effect and Efficacy of Anticancer Nanomedicine by Carbon Monoxide Generating Agents. Pharmaceutics 2019, 11, 343.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top