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EPR-Effect Enhancers Strongly Potentiate Tumor-Targeted Delivery of Nanomedicines to Advanced Cancers: Further Extension to Enhancement of the Therapeutic Effect

Authors :
Katsuhiko Ono
Jun Fang
Rayhanul Islam
Waliul Islam
Ayaka Harada
Shintaro Kimura
Takuro Niidome
Tomohiro Sawa
Hiroshi Maeda
Source :
Journal of Personalized Medicine, Journal of Personalized Medicine, Vol 11, Iss 487, p 487 (2021), Volume 11, Issue 6
Publication Year :
2021

Abstract

For more than three decades, enhanced permeability and retention (EPR)-effect-based nanomedicines have received considerable attention for tumor-selective treatment of solid tumors. However, treatment of advanced cancers remains a huge challenge in clinical situations because of occluded or embolized tumor blood vessels, which lead to so-called heterogeneity of the EPR effect. We previously developed a method to restore impaired blood flow in blood vessels by using nitric oxide donors and other agents called EPR-effect enhancers. Here, we show that two novel EPR-effect enhancers—isosorbide dinitrate (ISDN, Nitrol®) and sildenafil citrate—strongly potentiated delivery of three macromolecular drugs to tumors: a complex of poly(styrene-co-maleic acid) (SMA) and cisplatin, named Smaplatin® (chemotherapy)<br />poly(N-(2-hydroxypropyl)methacrylamide) polymer-conjugated zinc protoporphyrin (photodynamic therapy and imaging)<br />and SMA glucosamine-conjugated boric acid complex (boron neutron capture therapy). We tested these nanodrugs in mice with advanced C26 tumors. When these nanomedicines were administered together with ISDN or sildenafil, tumor delivery and thus positive therapeutic results increased two- to four-fold in tumors with diameters of 15 mm or more. These results confirmed the rationale for using EPR-effect enhancers to restore tumor blood flow. In conclusion, all EPR-effect enhancers tested showed great potential for application in cancer therapy.

Details

ISSN :
20754426
Volume :
11
Issue :
6
Database :
OpenAIRE
Journal :
Journal of personalized medicine
Accession number :
edsair.doi.dedup.....218ae5ccfd1201d90a1ac3a80fde3df3