Layer-by-Layer Nanoparticles of Tamoxifen and Resveratrol for Dual Drug Delivery System and Potential Triple-Negative Breast Cancer Treatment

Abstract

Nanoparticle development demonstrates use in various physicochemical, biological, and functional properties for biomedical applications, including anti-cancer applications. In the current study, a cancer therapeutic conjugate was produced consisting of tamoxifen (TAM) and resveratrol (RES) by layer-by-layer (LbL) nanoparticles based on lipid-based drug delivery systems and liquid crystalline nanoparticles (LCNPs) coated with multiple layers of positively charged chitosan and negatively charged hyaluronic acid for the evaluation of biocompatibility and therapeutic properties against cancer cells. Multiple techniques characterized the synthesis of TAM/RES–LbL-LCNPs, such as Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), Zeta potential analysis, particle size analysis, Field Emission Scanning Electron Microscope (FESEM), and Transmission electron microscopy (TEM). The in vitro cytotoxic effects of TAM/RES–LbL-LCNPs were investigated against human breast cancer cell line, Michigan Cancer Foundation-7 (MCF-7), and human triple-negative breast cancer cell line, Centre Antoine Lacassagne-51 (CAL-51), using various parameters. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed that the treatment of cells with TAM/RES–LbL-LCNPs caused a reduction in cell proliferation, and no such inhibition was observed with human normal liver cell line: American Type Culture Collection Cell Line-48 (WRL-68 [ATCC CL-48]). Fluorescent microscopy examined the ability of Fluorescein isothiocyanate (FITC) to bind to TAM/RES–LbL-LCNPs along with their cellular uptake. Apoptosis determination was performed using hematoxylin–eosin and acridine orange–propidium iodide double staining. The expression of P53 and caspase-8 was analyzed by flow cytometry analysis. An in vivo study determined the toxicity of TAM/RES–LbL-LCNPs in mice and assessed the functional marker changes in the liver and kidneys. No significant statistical differences were found for the tested indicators. TAM/RES–LbL-LCNP treatment showed no apparent damages or histopathological abnormalities in the heart, lung, liver, spleen, and kidney histological images. The current findings observed for the first time propose that TAM/RES–LbL-LCNPs provide a new and safer method to use phytochemicals in combinatorial therapy and provide a novel treatment approach against breast cancers.

Single-Cell Image-Based Analysis Reveals Chromatin Changes during the Acquisition of Tamoxifen Drug Resistance

“…An altered nuclear morphology is becoming one of the defining factors in cancer quantification, due to how this alteration can affect chromatin organization and function [ 59 , 60 ]. A condensed and fragmented cell nuclei was observed in tamoxifen-coated nanoparticle treated MCF7 cells [ 61 ]. The Tam-resistant cells that we used also exhibited a larger nuclear size and decreased eccentricity, which may have affected the chromatin dynamics of the nucleus.…”

Beneficial Oxidative Stress-Related trans-Resveratrol Effects in the Treatment and Prevention of Breast Cancer

“…Resveratrol was also delivered in conjunction with tamoxifen, a non-steroidal estrogen antagonist in ER+ breast cancer therapeutics, through layer-by-layer nanoparticles, which showed potent cytotoxicity and enhanced apoptosis in both MCF-7 and CAL-51 human breast cancer cell lines by increasing the expression of p53 and caspase-8 [114].…”

Investigating the Impact of Optimized Trans-Cinnamic Acid-Loaded PLGA Nanoparticles on Epithelial to Mesenchymal Transition in Breast Cancer

“… 14 Furthermore, other characteristics such as increased drug loading ability, longer half-life with mostly minor systemic toxicity, increased internalization into the tumor via endocytosis, sustained and regulated release of cytotoxic drug over the suitable duration and time along with body excretion are significant for nanoparticles in cancer treatment. 15 Biodegradable polymeric nanoparticles, lipid nanoparticles, magnetic nanoparticles, polymeric micelles, liposomes, niosomes, and nanoemulsions are all examples of nanotechnology formulation types. 16 The major drawbacks of most of the nanoparticle-based systems include low shelf‐life stability, the use of high concentrations of surfactant and cosurfactant, the liability of lipid oxidation and transformation, incompatibility with various active agents, and a limited drug loading efficiency.…”