Manganese nanocarrier for matrix metalloproteinase 9 responsive delivery of irinotecan for colon cancer treatment

다국어 초록 (Multilingual Abstract)

Enzyme responsive nanocarriers are reactive or sensitive towards a specific enzyme and, therefore, havethe 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 manganesenanocarrier for the site-specific delivery of anticancer drugs. Manganese nanoparticles werecoated with G5 PAMAM dendrimers and loaded with irinotecan hydrochloride (IRI). The drug loadednanoparticles were further coated with collagen-IV (Col-IV) peptide, an MMP9 substrate, to make themMMP9 responsive (Col-IV@IRI-G5MNP). The developed nanoparticles were monodispersed with size ofabout 12 nm and high IRI encapsulation efficiency (80%). A faster but controlled IRI release was observedfrom Col-IV@IRI-G5MNP in HEPES buffer containing MMP9 enzyme. When incubated with human redblood cells, the nanoformulation was hemocompatible and caused <2% hemolysis. The anticancer activityof Col-IV@IRI-G5MNP against HCT116 human colon cancer cells was better than free IRI. The cell viability ofHCT116 cells incubated with 25 lg/mL Col-IV@IRI-G5MNP was significantly lower (p < 0.001) than the cellsincubated with free IRI. Further, Col-IV@IRI-G5MNP showed paramagnetic nature and good T2 relaxivity ata very low concentration, suggesting its potential use for diagnosis through magnetic resonance imaging.