Co-Delivery of Ylang Ylang Oil of Cananga odorata and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer

Smart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean particle sizes lower than 170 nm and showed negative surface charges, high entrapment efficiencies, and a pH-dependent release over 24 h. The prepared pH-responsive niosomes’ cytotoxicity was tested against the invasive triple-negative breast cancer (MDA-MB-231) cells, compared to free OX and Y-oil. All niosomal formulations loaded with Ox and/or Y-oil significantly improved cytotoxic activity relative to their free counterparts. The Ox-Y@NSs demonstrated the lowest IC50 (0.0002 �g/mL) when compared to Ox@NSs (0.006 �g/mL) and Y@NSs (18.39 �g/mL) or unloaded Ox (0.05 �g/mL) and Y-oil (29.01 �g/mL). In addition, the percentages of theMDA-MB-231 cell population in the late apoptotic and necrotic quartiles were profoundly higher in cells treated with the smart Ox-Y@NSs (8.38% and 5.06%) than those exposed to free Ox (7.33% and 1.93%) or Y-oil (2.3% and 2.13%) treatments. Gene expression analysis and protein assays were performed to provide extra elucidation regarding the molecular mechanism by which the prepared pH-sensitive niosomes induce apoptosis. Ox-Y@NSs significantly induced the gene expression of the apoptotic markers Tp53, Bax, and Caspase-7, while downregulating the antiapoptotic Bcl2. As such, Ox-Y@NSs are shown to activate the intrinsic pathway of apoptosis. Moreover, the protein assay ascertained the apoptotic effects of Ox-Y@NSs, generating a 4-fold increase in the relative protein quantity of the late apoptotic marker Caspase-7. Our findings suggest that combining natural essential oil with synthetic platinum-based drugs in pH-responsive nanovesicles is a promising approach to breast cancer therapy

New proapoptotic chemotherapeutic agents based on the quinolone-3-carboxamide scaffold acting by VEGFR-2 inhibition

Abstract In the current study, we designed and synthesized a series of new quinoline derivatives 10a-p as antiproliferative agents targeting cancer through inhibition of VEGFR-2. Preliminary molecular docking to assess the interactions of the designed derivatives with the binding site of VEGFR-2 (PDB code: 4ASD) displayed binding poses and interactions comparable to sorafenib. The synthesized compounds exhibited VEGFR-2 inhibitory activity with IC50 ranging from 36 nM to 2.23 μM compared to sorafenib (IC50 = 45 nM), where derivative 10i was the most potent. Additionally, the synthesized derivatives were evaluated in vitro for their cytotoxic activity against HepG2 cancer cell line. Seven compounds 10a, 10c, 10d, 10e, 10i, 10n and 10o (IC50 = 4.60, 4.14, 1.07, 0.88, 1.60, 2.88 and 2.76 μM respectively) displayed better antiproliferative activity than sorafenib (IC50 = 8.38 μM). Compound 10i was tested against Transformed Human Liver Epithelial-2 normal cell line (THLE-2) to evaluate its selective cytotoxicity. Furthermore, 10i, as a potent representative of the series, was assayed for its apoptotic activity and cell cycle kinetics’ influence on HepG2, its effects on the gene expression of VEGFR-2, and protein expression of the apoptotic markers Caspase-7 and Bax. Compound 10i proved to have a potential role in apoptosis by causing significant increase in the early and late apoptotic quartiles, a remarkable activity in elevating the relative protein expression of Bax and Caspase-7 and a significant reduction of VEGFR-2 gene expression. Collectively, the obtained results indicate that compound 10i has a promising potential as a lead compound for the development of new anticancer agents

Box–Behnken design of thermo-responsive nano-liposomes loaded with a platinum( iv ) anticancer complex: evaluation of cytotoxicity and apoptotic pathways in triple negative breast cancer cells †

© 2023 The Author(s). Published by the Royal Society of Chemistry. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC), https://creativecommons.org/licenses/by-nc/4.0/Herein, thermo-responsive liposomes (TLs) loaded with Asp (Asp/TLs) were produced by self-assembling DPPC, DSPE-PEG2000, and cholesterol. The preparation variables were optimized using the Box–Behnken design (BBD). The optimized Asp/TLs exhibited an average particle size of 114.05 ± 1.56 nm, PDI of 0.15 ± 0.015, zeta potential of −15.24 ± 0.65 mV, and entrapment efficiency (EE%) of 84.08 ± 2.75%. In addition, under physiological conditions, Asp/TLs showed spherical shape, outstanding stability and thermo-triggered the release of Asp at 38 °C, reaching the maximum Asp release at 40 °C. The MTT assay showed that the optimal Asp/TLs exhibited the highest cytotoxic activity upon exposure to mild hyperthermia (40 °C) against the invasive triple-negative breast cancer cell line (MDA-MB-231) when compared to other preparations. The IC50 of Asp/TLs (40 °C) was estimated at 0.9 μg mL−1, while that of free Asp (40 °C) was 3.83 μg mL−1. As such, the optimal Asp/TLs were shown to increase the cytotoxic activity of Asp by 4-fold upon exposure to mild hyperthermia. The IC50 values of Asp and Asp/TLs without exposure to 40 °C were 6.6 μg mL−1 and 186 μg mL−1, respectively. This indicated that Asp was released only when placed at 40 °C. The apoptosis assay revealed that Asp/TLs (40 °C) caused a remarkable increase in the percentage of cell population among both the late apoptosis and necrosis quartiles, as well as a significant decline in the viable cell quartile (P ≤ 0.001) when compared to Asp (40 °C). Asp/TLs (40 °C) and Asp (40 °C) could stimulate the intrinsic apoptosis pathway by upregulating the apoptotic genes Bak and Bax, while downregulating the anti-apoptotic genes, BCL-xL and BCL-2. The free Asp (40 °C) increased the gene expression of Bak and Bax by 4.4- and 5.2-folds, while reducing the expression of BCL-xL and BCL-2 by 50% and 73%, respectively. The optimal Asp TLs (40 °C) manifested more potent effects as demonstrated by the upregulation of Bak, Bax, and P53 by 5.6-, 7.2-, and 1.3-folds, as well as the downregulation of BCL-xL and BCL-2 by 70% and 85%, respectively. As such, the optimal Asp TLs (40 °C) treatment displayed the most potent cytotoxic profile and induced both apoptosis and necrosis in MDA-MB-231.Peer reviewe

Kinetic, Isotherm and Thermodynamic Aspects of Zn²⁺ Biosorption by <i>Spirulina platensis</i>: Optimization of Process Variables by Response Surface Methodology

The aim of this study was to assess the efficiency of Spirulina platensis for removing Zn2+ ions from the aqueous solutions. The optimized conditions of 4.48 g/L algal dose, pH of 6.62 and initial zinc concentration of 29.72 mg/L obtained by response surface methodology were employed for Zn2+ biosorption by S. platensis and up to 97.90% Zn2+ was removed, showing that there is a favorable harmony between the experimental data and model predictions. Different kinetic and equilibrium models were used to characterize the biosorption manner of Spirulina as a biosorbent. The kinetic manner of Zn2+ biosorption was well characterized by the pseudo-second-order, implying that the adsorption process is chemical in nature. The Langmuir and Dubinin–Radushkevich isotherm models were best fit to the equilibrium data. The maximum adsorption capacity of the Langmuir monolayer was 50.7 mg/g. Furthermore, the thermodynamic analysis revealed that Zn2+ biosorption was endothermic, spontaneous and feasible. As a result of biosorption process, FTIR, SEM, and EDX investigations indicated noticeable alterations in the algal biomass’s properties. Therefore, the dried Spirulina biomass has been shown to be cost-effective and efficient for removing the heavy metals, particularly zinc ions from wastewater, and the method is practicable, and environmentally acceptable

Resveratrol Encapsulation and Release from Pristine and Functionalized Mesoporous Silica Carriers

Resveratrol, a naturally occurring polyphenol, has attracted significant attention due to its antioxidant, cardioprotective and anticancer potential. However, its low aqueous solubility limits resveratrol bioavailability and use. In this work, different mesoporous silica matrices were used to encapsulate the polyphenol and to increase its dissolution rate. Pristine MCM-41, MCM-48, SBA-15, SBA-16, FDU-12 and MCF silica were obtained. The influence of SBA-15 functionalized with aminopropyl, isocyanate, phenyl, mercaptopropyl, and propionic acid moieties on resveratrol loading and release profiles was also assessed. The cytotoxic effects were evaluated for mesoporous carriers and resveratrol-loaded samples against human lung cancer (A549), breast cancer (MDA-MB-231) and human skin fibroblast (HSF) cell lines. The effect on apoptosis and cell cycle were assayed for selected resveratrol-loaded carriers. The polyphenol molecules are encapsulated only inside the mesopores, mostly in amorphous state. All materials containing either pristine or functionalized silica carriers increased polyphenol dissolution rate. The influence of the physico-chemical properties of the mesoporous carriers and resveratrol–loaded supports on the kinetic parameters was identified. Resv@SBA-15-SH and Resv@SBA-15-NCO samples exhibited the highest anticancer effect against A549 cells (IC50 values were 26.06 and 36.5 µg/mL, respectively) and against MDA-MB-231 (IC50 values were 35.56 and 19.30 µg/mL, respectively), which highlights their potential use against cancer

The Antioxidant and Anti-Inflammatory Properties of Wild Bilberry Fruit Extracts Embedded in Mesoporous Silica-Type Supports: A Stability Study

Polyphenolic extracts from wild bilberries (Vaccinium myrtillus L.) have shown antioxidant and anti-inflammatory effects, but they are prone to degradation when exposed to environmental factors, limiting their use in biomedical applications. To overcome this issue, this study proposed the embedding of wild bilberry fruit ethanolic extracts in pristine mesoporous silica functionalized with organic groups (mercaptopropyl and propionic acid), as well as coated with fucoidan, a biopolymer. Herein, we report a stability study of free and incorporated extracts in mesoporous silica-type supports in high-humidity atmospheres at 40 °C up to 28 days, using HPLC analysis, thermal analysis, and radical scavenging activity determination. Better chemical and thermal stability over time was observed when the extracts were incorporated in mesoporous silica-type supports. After 12 months of storage, higher values of antioxidant activity were determined for the extract embedded in the supports, silica modified with mercaptopropyl groups (MCM-SH), and fucoidan-coated silica (MCM-SH-Fuc) than that of the free extract due to a synergistic activity between the support and extract. All encapsulated extracts demonstrated remarkable effects in reducing NO production in LPS-stimulated RAW 264.7 cells. The treatment with extract embedded in MCM-SH-Fuc in a dose of 10 μg/mL surpassed the effect of free extract in the same concentration. For the extract encapsulated in an MCM-SH support, a lower IC50 value (0.69 μg/mL) towards COX-2 was obtained, comparable with that of Indomethacin (0.6 μg/mL). Also, this sample showed a higher selectivity index (2.71) for COX-2 than the reference anti-inflammatory drug (0.98). The developed formulations with antioxidant and anti-inflammatory properties could be further used in nutraceuticals

The medicinal activity of lyophilized aqueous seed extract of Lepidium sativum L. in an androgenic alopecia model

Abstract This study evaluated the topical effect of Lepidium sativum lyophilized seed extract (LSLE) towards Sustanon-induced alopecia in male adult Wistar albino rats in vivo, compared to minoxidil topical reference standard drug (MRD). LC–MS/MS together with molecular networking was used to profile the metabolites of LSLE. LSLE treated group revealed significant changes in alopecia related biomarkers, perturbation of androgenic markers; decline in testosterone level and elevation in 5α-reductase (5-AR); decline in the cholesterol level. On the other hand, LSLE treated group showed improvement in vascular markers; CTGF, FGF and VEGF. Groups treated topically with minoxidil and LSLE showed significant improvement in hair length. LC–MS/MS profile of LSLE tentatively identified 17 constituents: mainly glucosinolates, flavonoid glycosides, alkaloids and phenolic acids. The results point to the potential role of LSLE in the treatment of alopecia through decreasing 5(alpha)-dihydrotestosterone levels. Molecular docking was attempted to evaluate the probable binding mode of identified compounds to androgen receptor (PDB code: 4K7A)