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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
- 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.
- Subjects :
- Sildenafil
medicine.medical_treatment
Medicine (miscellaneous)
Photodynamic therapy
EPR-effect enhancers
sildenafil citrate
heterogeneity of the EPR effect
Article
Nitric oxide
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
nitric oxide donors
medicine
tumor blood flow
030304 developmental biology
Cisplatin
0303 health sciences
Chemotherapy
business.industry
Therapeutic effect
Zinc protoporphyrin
EPR effect
SMA
isosorbide dinitrate
chemistry
030220 oncology & carcinogenesis
Cancer research
Medicine
business
medicine.drug
Subjects
Details
- ISSN :
- 20754426
- Volume :
- 11
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of personalized medicine
- Accession number :
- edsair.doi.dedup.....218ae5ccfd1201d90a1ac3a80fde3df3