biostudies-literatureIslam WMinistry of Health, Labour and WelfareJapan Science and Technology AgencyJapan Society for the Promotion of Science487https://www.ebi.ac.uk/biostudies/studies/S-EPMC8229906biostudies-literatureUnknown11(6)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® (chJournal of personalized medicineEPR-Effect Enhancers Strongly Potentiate Tumor-Targeted Delivery of Nanomedicines to Advanced Cancers: Further Extension to Enhancement of the Therapeutic Effect.PMC82299062940000117016076AS242Z01542QGeneral 00118H04059Niidome TMaeda HIslam RFang JKimura SIslam WOno KHarada ASawa TfalseEPR-Effect Enhancers Strongly Potentiate Tumor-Targeted Delivery of Nanomedicines to Advanced Cancers: Further Extension to Enhancement of the Therapeutic Effect.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® (ch2021-01-01T00:00:00Z2021 May2025-04-19T17:43:34.341Z2022-02-10T18:48:43.173ZS-EPMC82299063407155210.3390/jpm11060487