Fabrication of folic acid-conjugated chitosan-coated PLGA nanoparticles for targeted delivery of Peganum harmala smoke extract to breast cancer cells

Abstract

In this study, PLGA-NPs coated with folic acid-chitosan (PCF-NPs) loaded with Peganum harmala smoke extract (PSE) were synthesized (PSE-PCF-NPs), and their anti-cancer effects were evaluated. PSE-PCF-NPs were synthesized by the nanoprecipitation method and then characterized by DLS, SEM, and FTIR methods. HPLC and UV–vis spectroscopy were used to evaluate the PSE’s folic acid (FA) binding and encapsulation. PSE-PCF-NPs-mediated cell viability and apoptosis were investigated by MTT, qPCR, flow cytometry, AO/PI, and DAPI staining. Anti-oxidant properties of PSE-PCF-NPs were evaluated by ABTS, DPPH, FRAP, and ROS. Angiogenic effects of PSE-PCF-NPs were assessed by CAM assay. The PSE-PCF-NPs (276.16 nm, PDI: 0.25, zeta-potential: +32.31 mV, FB: 67.6% and %EE: 89%) demonstrated selective toxicity on MCF-7 cells (IC50: 75.65 μg ml−1). The occurrence of apoptosis in MCF-7 cells was confirmed by up-regulation of P53, Cas-3, and Cas-9 genes, increased SubG1 phase cells, and the results of fluorescent staining. Scavenging free radicals, reducing iron ions, increasing intracellular ROS, and decreasing SOD gene confirmed the anti- and pro-oxidant effects of PSE-PCF-NPs outside and inside MCF-7 cells. Reduction of angiogenic factors in CAM assay showed the anti-angiogenic effects of PSE-PCF-NPs. PSE-PCF-NPs, due to their anti-cancer properties, can be considered a therapeutic agent in cancer studies.

Evaluation of the effect of designed PLGA‐arctiin nanoparticles modified with folic acid and chitosan on colon cancer cells

“…Moreover, the results showed that ARC‐PCF‐NPs have a remarkable inhibitory effect on Gram‐positive bacteria. Similarly, a study with the synthesis of PLGA NPs coated with CS and FA containing Peganum harmala smoke extract found that these NPs scavenge ABTS and DPPH free radicals, decrease ferrous in FRAP test, increase intracellular reactive oxygen species, and decrease the expression of SOD gene in breast cancer cells 29 . In addition, Alirezaei et al.…”

“…Similarly, a study with the synthesis of PLGA NPs coated with CS and FA containing Peganum harmala smoke extract found that these NPs scavenge ABTS and DPPH free radicals, decrease ferrous in FRAP test, increase intracellular reactive oxygen species, and decrease the expression of SOD gene in breast cancer cells. 29 In addition, Alirezaei et al used PLGA-based NPs modified with CS-FA in order to optimize the antitumor effects of Dermina vulgaris essential oil. They found that these NPs increase apoptosis and inhibit the angiogenesis of HT-29 cancer cells.…”

Design of Chitosan-Coated, Quercetin-Loaded PLGA Nanoparticles for Enhanced PSMA-Specific Activity on LnCap Prostate Cancer Cells

“…As expected, there is no significant difference in fluorescence between the coated and uncoated nanoparticle treatments on the PC-3 cell line ( Figure 9 (B1,B2)) and Table 5 . This suggests a greater selective uptake of the coated nanoparticles by the PSMA-positive LnCap cell line compared with the PSMA-negative PC-3 cell line, which could be facilitated by the binding of the PSMA receptors on the LnCap cells by the folic acid moieties on the surface of the coated nanoparticles, allowing them to enter the cells by receptor-mediated endocytosis [ 52 , 55 , 56 ].…”