Dual functional matrix metalloproteinase-responsive curcumin-loadednanoparticles for tumor-targeted treatment

摘要

The limitations of anticancer drugs, including poor tumor targeting and weak uptakeefficiency, are important factors affecting tumor therapy. According to characteristics ofthe tumor microenvironment, in this study, we aimed to synthesize matrix metalloproteinase(MMP)-responsive curcumin (Cur)-loaded nanoparticles (Cur-P-NPs) based on amphiphilicblock copolymer (MePEG-peptide-PET-PCL) with MMP-cleavable peptide (GPLGIAGQ) andpenetrating peptide (r9), modified to improve tumor targeting and cellular uptake. Theaverage size of Cur-P-NPs was 176.9 nm, with a zeta potential of 8.1 mV, and they showeddrug entrapment efficiency and a loading capacity of 87.07% ± 0.63% and 7.44% ± 0.16%,respectively. Furthermore, Cur release from Cur-P-NPs was sustained for 144 h at pH 7.4,and the release rate was accelerated under enzyme reaction condition. The MTT assaydemonstrated that free P-NPs had favorable biosafety, and the anti-proliferative activityof Cur-P-NPs was positively correlated with Cur concentration in MCF-7 cells.Additionally, the results of cellular uptake, in vivo pharmacokinetics, andbiodistribution showed that Cur-P-NPs had a good effect on cellular uptake and tumortargeting, resulting in the best bioavailability in tumor therapy. Therefore, Cur-P-NPs,as a promising drug delivery system, might lead to a new and efficient route for targetedtherapy in clinical practice.