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Abstract
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.
Graphical Abstract
Acknowledgments
The authors thank the Central University of Gujarat and Central Instrument Facility for providing laboratory facilities. H.K. acknowledges the Early Career Research Award by the SERB, DST, New Delhi and INSPIRE Faculty Award by the DST, New Delhi. S.C., K.P., P.J., and A.K.J. acknowledge the University Grant Commission, New Delhi for PhD Fellowships. The authors gratefully acknowledge the UGC-DAE Consortium for Scientific Research, Indore, M.P., India, for XPS measurements.
Disclosure statement
No potential conflict of interest was reported by the author(s).