Enhanced Efficacy of Doxorubicin by microRNA-499-Mediated Improvement of Tumor Blood Flow

Journal of Clinical Medicine
Ayaka OkamotoNaoto Oku

Abstract

Genetic therapy using microRNA-499 (miR-499) was combined with chemotherapy for the advanced treatment of cancer. Our previous study showed that miR-499 suppressed tumor growth through the inhibition of vascular endothelial growth factor (VEGF) production and subsequent angiogenesis. In the present study, we focused on blood flow in tumors treated with miR499, since some angiogenic vessels are known to lack blood flow. Tetraethylenepentamine-based polycation liposomes (TEPA-PCL) were prepared and modified with Ala-Pro-Arg-Pro-Gly peptide (APRPG) for targeted delivery of miR-499 (APRPG-miR-499) to angiogenic vessels and tumor cells. The tumor blood flow was significantly improved, so-called normalized, after systemic administration of APRPG-miR-499 to Colon 26 NL-17 carcinoma-bearing mice. In addition, the accumulation of doxorubicin (DOX) in the tumors was increased by pre-treatment with APRPG-miR-499. Moreover, the combination therapy of APRPG-miR-499 and DOX resulted in significant suppression of the tumors. Taken together, our present data indicate that miR-499 delivered with APRPG-modified-TEPA-PCL normalized tumor vessels, resulting in enhancement of intratumoral accumulation of DOX. Our findings suggest that APRPG-miR-499...Continue Reading

References

Jan 23, 1987·Science·J Folkman, M Klagsbrun
Jan 1, 1987·Nouvelle Revue Française D'hématologie·A Camez, G Tobelem
Nov 18, 1971·The New England Journal of Medicine·J Folkman
Jul 1, 1994·Scientific American·R K Jain
Jun 12, 2003·British Journal of Cancer·H WildiersA T van Oosterom
Jun 4, 2004·The New England Journal of Medicine·Herbert HurwitzFairooz Kabbinavar
Dec 21, 2004·Cancer Cell·Michelle I Lin, William C Sessa
Jun 15, 2007·Microvascular Research·Dai Fukumura, Rakesh K Jain
Jul 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aurelia Walczak-DrzewieckaJaroslaw Dastych
Feb 5, 2010·Journal of Cancer Research and Clinical Oncology·Guichun Huang, Longbang Chen
Aug 17, 2010·Cytokine·Madhi Saranadasa, Eunice S Wang
Aug 25, 2010·Circulation. Cardiovascular Genetics·Kitchener D WilsonJoseph C Wu
Mar 3, 2011·Bioconjugate Chemistry·Tomohiro AsaiNaoto Oku
Apr 3, 2012·Biochemical and Biophysical Research Communications·Lu-lu ZhangBo Yu
Dec 15, 2012·The Journal of Gene Medicine·Hidenori AndoNaoto Oku
Oct 10, 2013·The Journal of Gene Medicine·Hidenori AndoNaoto Oku
Mar 7, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hidenori AndoNaoto Oku
Jan 24, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fuman QiuJiachun Lu
Jan 28, 2015·Proceedings of the National Academy of Sciences of the United States of America·Meenal DattaRakesh K Jain

❮ Previous
Next ❯

Citations

Aug 20, 2016·Advanced Drug Delivery Reviews·Huihui KuangEfrosini Kokkoli
Sep 6, 2017·Respiratory Research·Judit RappJudit E Pongracz
Oct 4, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jafrin Jobayer SonjuSeetharama D Jois

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Related Papers

Journal of Controlled Release : Official Journal of the Controlled Release Society
Hidenori AndoNaoto Oku
International Journal of Pharmaceutics
Yasufumi KatanasakaNaoto Oku
Journal of Controlled Release : Official Journal of the Controlled Release Society
Noriyuki MaedaNaoto Oku
© 2022 Meta ULC. All rights reserved