Augmentation of the Enhanced Permeability and Retention Effect with Nitric Oxide-Generating Agents Improves the Therapeutic Effects of Nanomedicines

Molecular Cancer Therapeutics
Waliul IslamHiroshi Maeda

Abstract

Enhanced permeability and retention (EPR) effect-based nanomedicine is a promising strategy for successful anticancer therapy. The EPR effect is based on tumor blood flow. Because advanced large tumors, as frequently seen in clinical settings, are heterogeneous, with regions of defective vasculature and blood flow, achieving the desired tumor drug delivery is difficult. Here, we utilized the EPR effect to increase drug delivery. To augment the EPR effect for improved therapeutic effects of nanomedicine, we exploited vascular mediators-the nitric oxide (NO) generators nitroglycerin (NG), hydroxyurea, and l-arginine. These compounds generate NO in tumors with relatively high selectivity. Using different nanosized drugs in our protocol significantly increased (1.5-2 times) delivery of nanomedicines to different solid tumor models, along with markedly improving (2-3-fold) the antitumor effects of these drugs. Also, in 7,12-dimethylbenz[a]anthracene-induced advanced end-stage breast cancer, often seen in clinical settings, 2 mg/kg polymer-conjugated pirarubicin (P-THP) with NG (0.2 mg/mouse) showed better effects than did 5 mg/kg P-THP, and 5 mg/kg P-THP used with NG resulted in cures or stable tumors (no tumor growth) for up to 120...Continue Reading

References

Jan 13, 1998·Molecular Pharmacology·J JiangR P Mason
Apr 3, 1999·Journal of Pharmaceutical Sciences·T ShinodaM Hashida
May 11, 2001·Japanese Journal of Cancer Research : Gann·J WuH Maeda
Mar 18, 2003·International Immunopharmacology·Hiroshi MaedaYasunori Kitamoto
Apr 15, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hyuk Sang Yoo, Tae Gwan Park
Nov 24, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hiroyasu YasudaMutsuo Yamaya
Feb 7, 2009·The New England Journal of Medicine·Jolien TolCornelis J A Punt
Mar 12, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·A Cirstoiu-HapcaF Delie
Mar 23, 2010·Advanced Drug Delivery Reviews·Vladimir Torchilin
Jun 21, 2011·Nature Materials·Geoffrey von MaltzahnSangeeta N Bhatia
Sep 29, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Twan LammersGert Storm
Feb 24, 2012·The New England Journal of Medicine·Jeffrey A SosmanAntoni Ribas
Mar 9, 2012·The New England Journal of Medicine·Marco GerlingerCharles Swanton
Jun 28, 2012·Molecular Pharmaceutics·Niladri ChattopadhyayRaymond M Reilly
Jul 18, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Il Keun KwonKinam Park
Dec 12, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hideaki NakamuraHiroshi Maeda
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Nov 26, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hideaki NakamuraHiroshi Maeda
May 14, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ruth Duncan
Sep 4, 2015·Redox Biology·Federica VanniniNiharika Nath
May 22, 2017·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Tomáš EtrychHiroshi Maeda
Oct 11, 2017·Journal of Drug Targeting·Hiroshi Maeda
Jun 11, 2018·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Jun FangHiroshi Maeda

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Citations

Apr 18, 2019·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Steffen HackbarthHiroshi Maeda
Jul 3, 2020·Chemical & Pharmaceutical Bulletin·Yu IshimaTatsuhiro Ishida
Aug 15, 2020·Expert Opinion on Drug Delivery·L Gallego, V Ceña
Sep 4, 2020·Biological & Pharmaceutical Bulletin·Haitao FengYoshiki Katayama
Sep 20, 2019·Antioxidants·Emily Hays, Benjamin Bonavida
Aug 11, 2020·Journal of Drug Targeting·Sepideh NezhadiFarid Dorkoosh
Aug 23, 2020·International Journal of Molecular Sciences·Wioletta OlejarzTomasz Lorenc
Aug 30, 2020·Antioxidants·Long Binh Vong, Yukio Nagasaki
Jul 7, 2020·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Haitao FengYoshiki Katayama
Aug 1, 2020·Advanced Drug Delivery Reviews·Jindřich Kopeček, Jiyuan Yang
Feb 14, 2021·Journal of Personalized Medicine·Petr ChytilTomáš Etrych
Apr 26, 2020·Drug Discovery Today·Sarita Rani, Umesh Gupta
Apr 1, 2021·Molecular Pharmaceutics·Alessandra SpadaAfsaneh Lavasanifar
Jul 3, 2021·Journal of Personalized Medicine·Md Abdus SubhanVladimir P Torchilin
Jul 17, 2021·Acta Biomaterialia·Ying Zhang, Jingni He
Jul 19, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yajie ZhangYong Ma
Jan 13, 2022·International Journal of Radiation Biology·Thao Anh TranMartin Purschke

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