Dual functional matrix metalloproteinase-responsive curcumin-loaded nanoparticles for tumor-targeted treatment

Abstract

The limitations of anticancer drugs, including poor tumor targeting and weak uptake efficiency, are important factors affecting tumor therapy. According to characteristics of the tumor microenvironment, in this study, we aimed to synthesize matrix metalloproteinase (MMP)-responsive curcumin (Cur)-loaded nanoparticles (Cur-P-NPs) based on amphiphilic block copolymer (MePEG-peptide-PET-PCL) with MMP-cleavable peptide (GPLGIAGQ) and penetrating peptide (r9), modified to improve tumor targeting and cellular uptake. The average size of Cur-P-NPs was 176.9 nm, with a zeta potential of 8.1 mV, and they showed drug 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 assay demonstrated that free P-NPs had favorable biosafety, and the anti-proliferative activity of Cur-P-NPs was positively correlated with Cur concentration in MCF-7 cells. Additionally, the results of cellular uptake, in vivo pharmacokinetics, and biodistribution showed that Cur-P-NPs had a good effect on cellular uptake and tumor targeting, 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 targeted therapy in clinical practice.

Star polyester-based folate acid-targeting nanoparticles for doxorubicin and curcumin co-delivery to combat multidrug-resistant breast cancer

“…As the DOX concentration increased (40–80 μg/mL), (DOX + CUR)-FA-NPs and (DOX + CUR)-NPs showed better anti-proliferative abilities than (DOX + CUR). In this phase, as the drug content increased, more (DOX + CUR)-loaded nanocarriers were taken up into the cells because of an increased cell-uptake efficiency (Guo et al, 2019 ).…”

“…However, the emergence of MDR (by the P-gp pathway; Li et al, 2018 ), strong cell toxicity, and poor targeting selection have seriously hindered its clinical application. Curcumin (CUR) is a low-toxicity natural drug made of polyphenols extracted from Zingiberaceae plants (Wu et al, 2019 ) and is less effective against cancer than first-line chemotherapy but has broad-spectrum effects (Guo et al, 2018 ; Zhang et al, 2018 ; Barati et al, 2019 ; Guo et al, 2019 , 2020 ). Hou et al ( 2019 ) and Lv et al ( 2016 ) have shown that CUR is an excellent P-gp inhibitor that effectively maintains a high DOX concentration in drug-resistant human breast cancer MCF-7/ADR cells.…”

The role of cell‐penetrating peptides in potential anti‐cancer therapy

“…In vivo pharmacokinetics demonstrated that CUR-P-NPs are more targeted to MCF-7 xenografts than normal tissues, causing significant increase in bioavailability. 156…”

“…In another recent study, the tumour‐targeting mechanism and the effect of the cellular uptake of MMP‐reactive CUR NPs on the breast cancer cell line MCF‐7 were analysed in vivo and in vitro, respectively. In vivo pharmacokinetics demonstrated that CUR‐P‐NPs are more targeted to MCF‐7 xenografts than normal tissues, causing significant increase in bioavailability 156 …”

The roles of curcumin in regulating the tumor immunosuppressive microenvironment (Review)

“…To address these problems, an increasing numbers of studies are focusing on how to enhance the tolerance of curcumin, improve the targeting of curcumin delivery, overcome low bioavailability and obtain better therapeutic effects (124,125). A variety of nano-curcumin formulations have been introduced, which have improved the anti-cancer effects of curcumin (126,127). It is considered that curcumin will serve a more important role in the prevention and treatment of cancer in the future.…”