Abstract
Enzyme responsive nanocarriers are reactive or sensitive towards a specific enzyme and, therefore, have the advantages of low systemic toxicity, targeted delivery, and superior therapeutic effect with high efficiency. In this study, we have developed a matrix metalloproteinase 9 (MMP9) enzyme responsive manganese nanocarrier for the site-specific delivery of anticancer drugs. Manganese nanoparticles were coated with G5 PAMAM dendrimers and loaded with irinotecan hydrochloride (IRI). The drug loaded nanoparticles were further coated with collagen-IV (Col-IV) peptide, an MMP9 substrate, to make them MMP9 responsive (Col-IV@IRI-G5MNP). The developed nanoparticles were monodispersed with size of about 12 nm and high IRI encapsulation efficiency (80%). A faster but controlled IRI release was observed from Col-IV@IRI-G5MNP in HEPES buffer containing MMP9 enzyme. When incubated with human red blood cells, the nanoformulation was hemocompatible and caused <2% hemolysis. The anticancer activity of Col-IV@IRI-G5MNP against HCT116 human colon cancer cells was better than free IRI. The cell viability of HCT116 cells incubated with 25 µg/mL Col-IV@IRI-G5MNP was significantly lower (p < 0.001) than the cells incubated with free IRI. Further, Col-IV@IRI-G5MNP showed paramagnetic nature and good T2 relaxivity at a very low concentration, suggesting its potential use for diagnosis through magnetic resonance imaging.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.