Matrix metalloproteinase enzyme responsive delivery of 5-Fluorouracil using Collagen-I peptide functionalized Dendrimer-Gold nanocarrier.

OBJECTIVE: The aim was to develop matrix metalloproteinase 1 (MMP1) responsive nanoparticle system for the delivery of 5-fluorouracil (5Fu) anticancer drug. SIGNIFICANCE: The MMP1 in the cancer microenvironment-induced drug release have the advantage of targeted drug release and reduce the distribution of drug to the healthy tissues. METHOD: G5 poly(amidoamine) (PAMAM) dendrimer (G5)-coated gold nanoparticles (G5AuNP) were synthesized and loaded with 5Fu. The drug-loaded nanoparticles were further coated with collagen I (Col-I) peptide, which is a substrate for MMP1 enzyme (Col-I 5Fu@G5AuNP). RESULT: The nanoparticles were highly monodispersed with a particle size of 30 nm and showed high drug encapsulation efficiency. The release of drug from the nanoparticles in HEPES buffer pH 7.4 was faster, higher and better controlled when incubated with MMP1 enzyme. The half-maximum inhibitory concentration for Col-I 5Fu@G5AuNP was eight times lower than the 5Fu against MCF-7, suggesting the improved delivery and anticancer activity of 5Fu after encapsulation in the developed enzyme-responsive nanocarrier system. The computed tomography (CT) X-ray attenuation of Col-I@G5AuNP showed a good contrasting property. CONCLUSION: The formulation Col-I 5Fu@G5AuNP has improved anticancer activity than free drug and the CT imaging results are promising for its theranostic applications for breast cancer treatment.

Effect of recombinant malarial antigen on monocyte functionality.

BACKGROUND: Recombinant proteins and vaccine candidates of Plasmodium vivax have met with limited success. One of the reasons could be their effect on monocytes which are important in malaria pathogenesis. Our aim was therefore to investigate the effect of selected recombinant malarial proteins on monocytes functions. METHODS: Phagocytosis rate and respiratory burst of healthy individuals' monocytes treated with antigens were examined. The homing capacity of monocytes was studied by examining the mRNA level of chemokine receptors from patients and healthy individuals. RESULTS: Phagocytosis rate was reduced in antigen treated monocytes whereas nitroblue tetrazolium (NBT) reduction was more in apical membrane antigen-1 (AMA-1) and merozoite surface protein-7 (MSP7) treated than in untreated and von Willebrand factor A domain-related protein (WARP) treated monocytes. Patient monocytes showed higher mRNA expression for CCR2 and CX3CR1 and reduced levels for CCR7 and CXCR4. AMA-1 and WARP treated monocytes showed lower expression for CCR2, CX3CR1 and CXCR4, but unchanged for CCR7. However, with MSP7, all the receptor levels were reduced. CX3CR1 in monocytes from activated PBMCs was either unchanged (AMA-1) or increased (MSP7, WARP) while remaining receptors were reduced. CONCLUSIONS: These antigens may modulate the monocyte functionality and hence may not have desired therapeutic effect.