Development of PEGylated PLGA Nanoparticles Co-Loaded with Bioactive Compounds: Potential Anticancer Effect on Breast Cancer Cell Lines

Abstract

Objective:The incidence of breast cancer continues to rise despite decades of laboratory, epidemiological and clinical research. Breast cancer is still the leading cause of cancer death in women. Cyclin D1 is one of the most important oncoproteins associated with cancer cell proliferation and is overexpressed in more than 50% of cases. Curcumin and chrysin are plant-derived components that are believed to assist in inhibiting the viability of breast cancer cells. These agents are involved in cancer cells' growth and reducing cyclin D1 expression. In this study, the hypothesis of combining curcumin and chrysin is applied to analyze the potential synergistic effect in inhibiting cancer cell proliferation and down-regulation of cyclin D1. Furthermore, applying PLGA-PEG NPs could improve the bioavailability of free curcumin and chrysin components and at the same time increases the anti-cancer potential of this compound. Methods: PLGA-PEG NPs were synthesized via the ring-opening polymerization technique and characterized with FT-IR and FE-SEM for chemical structure and morphological characteristics, respectively. Next, curcumin and chrysin were loaded in PLGA-PEG NPs and MTT assay was performed to assess the cytotoxic effect of these agents. T-47D cells were treated with appropriate concentrations of these agents and cyclin D1 expression level was evaluated by real-time PCR. Results: The obtained results from FT-IR and FE-SEM techniques illustrated that curcumin and chrysin were efficiently encapsulated into PLGA-PEG NPs. Curcumin, chrysin, and curcumin-chrysin in free and nano-encapsulated forms exhibited an anti-cancer effect on T-47D cells in a time-and dose-dependent manner, especially in a combination of free and encapsulated forms demonstrated synergistic anti-cancer effects. Compared to free form, Nano-curcumin, Nano-chrysin, and Nano-combination remarkably down-regulated cyclin D1 gene expression. (p-value < 0.05). Conclusion: Our results revealed that the curcumin-chrysin combination has a synergistic effect and the encapsulated form of this nano-component has more inhibition on cyclin D1 expression.

Fabricating niosomal-PEG nanoparticles co-loaded with metformin and silibinin for effective treatment of human lung cancer cells

“…It suggests that by improving MET’s and SIL’s solubility and bioavailability, this form of drug delivery system could enhance its transport to cancer cells ( 48 ). The findings of our investigation are in agreement with those of former research that has shown that MET and SIL inhibit the growth and proliferation of the A549 cell line ( 52 – 54 ).…”

Quercetin, a Flavonoid with Great Pharmacological Capacity

“…In vivo, studies with human leukemia 60 (HL-60) cells report that concentrations between 20 and 30 µM are sufficient to exert an inhibitory effect on cytosolic PKC activity and membrane tyrosine protein kinase (TPK) activity. Within the same study, it is noted that a concentration of 80 µM is sufficient to block the activity of phosphatidylinositol (4,5) bisphosphate [75]. On the other hand, it has been shown that quercetin induces the inactivation of the AKT protein, an antiapoptotic protein, by decreasing its phosphorylation and also directly inactivates procaspase 9, thus blocking Another pathway susceptible to quercetin action is the protein kinase C (PKC) pathway, which is also downregulated [73]; by blocking the diacylglycerol (DAG) precursor of PKC, inhibition of this pathway leads to blocking the formation of phosphatidylinositol (3,4,5)trisphosphate, which activates the entry of extracellular calcium [74].…”

“…In vivo, studies with human leukemia 60 (HL-60) cells report that concentrations between 20 and 30 µM are sufficient to exert an inhibitory effect on cytosolic PKC activity and membrane tyrosine protein kinase (TPK) activity. Within the same study, it is noted that a concentration of 80 µM is sufficient to block the activity of phosphatidylinositol (4,5) bisphosphate [ 75 ]. On the other hand, it has been shown that quercetin induces the inactivation of the AKT protein, an antiapoptotic protein, by decreasing its phosphorylation and also directly inactivates procaspase 9, thus blocking cellular apoptosis [ 76 ].…”

Preparation of PLGA microspheres loaded with niclosamide via microfluidic technology and their inhibition of Caco-2 cell activity in vitro

“…CD44 is closely related to the growth, infiltration, and metastasis of tumors, thereby inducing cell apoptosis. Functional PLGA drug delivery systems can also improve the inhibition of the proliferation of Caco-2 cells by regulating their cell cycles ( Luo et al, 2019 ; Moghaddam et al, 2021 ; Mohammadinejad et al, 2022 ). PLGA can release drugs in vivo and in vitro through mechanisms such as degradation into water-soluble lactic acid and glycolic acid, and surface erosion, thereby changing the cell environment and affecting the cell cycle.…”