Several studies have indicated the potential therapeutic outcomes of combining selective COX-2 inhibitors with tubulin-targeting anticancer agents. In the current study, a novel series of thiazolidin-4-one-based derivatives (7a–q) was designed by merging the pharmacophoric features of some COXs inhibitors and tubulin polymerization inhibitors. Compounds 7a–q were synthesized and evaluated for their cytotoxic activity against MCF7, HT29, and A2780 cancer cell lines (IC₅₀ = 0.02–17.02 μM). The cytotoxicity of 7a–q was also assessed against normal MRC5 cells (IC₅₀ = 0.47–13.46 μM). Compounds 7c, 7i, and 7j, the most active in the MTT assay, significantly reduced the number of HT29 colonies compared to the control. Compounds 7c, 7i, and 7j also induced significant decreases in the tumor volumes and masses in Ehrlich solid carcinoma-bearing mice compared to the control. The three compounds

A small set of indole-based derivatives, IV and Va–I, was designed and synthesized. Compounds Va–i demonstrated promising antiproliferative activity, with GI₅₀ values ranging from 26 nM to 86 nM compared to erlotinib’s 33 nM. The most potent antiproliferative derivatives—Va, Ve, Vf, Vg, and Vh—were tested for EGFR inhibitory activity. Compound Va demonstrated the highest inhibitory activity against EGFR with an IC₅₀ value of 71 ± 06 nM, which is higher than the reference erlotinib (IC₅₀ = 80 ± 05 nM). Compounds Va, Ve, Vf, Vg, and Vh were further tested for BRAF^V600E inhibitory activity. The tested compounds inhibited BRAF^V600E with IC₅₀ values ranging from 77 nM to 107 nM compared to erlotinib’s IC₅₀ value of 60 nM. The inhibitory activity of compounds Va, Ve, Vf, Vg, and Vh against VEGFR-2 was also determined. Finally, in silico docking experiments attempted to investigate the binding mode of compounds within the active sites of EGFR, BRAF^V600E, and VEGFR-2.

A new series of 5-substituted-3-ethylindole-2-carboxamides 5a–k and 6a–c was designed and synthesised
in an attempt to develop a dual targeted antiproliferative agent. Various spectroscopic methods of analysis
were used to confirm the structures of the new compounds. The antiproliferative effect of compounds
5a–k and 6a–c against four cancer cell lines was investigated. Compounds 5a–k and 6a–c had significant
antiproliferative activity against the four cancer cell lines tested, with mean GI50 values ranging from 37 nM
to 193 nM. The most powerful derivatives were compounds 5g, 5i, and 5j, with GI50 values of 55 nM, 49
nM, and 37 nM, respectively, in comparison to the reference erlotinib, which had a GI50 of 33 nM. The four
most potent compounds, 5c, 5g, 5i, and 5j, were then investigated for their efficacy as EGFR inhibitors, and
the findings showed that the tested compounds inhibited EGFR with IC50 values ranging from 85 nM to
124 nM when compared to the reference erlotinib (IC50 = 80 nM). Moreover, compounds 5c and 5g
inhibited CDK2 with IC50 values of 46 ± 05 nM and 33 ± 04 nM, respectively. The EGFR and CDK2 assays
revealed that compounds 5i and 5j displayed potent antiproliferative activity and can be considered as
potential dual EGFR and CDK2 inhibitors.

Breast cancer is a wide-spread threat to the women’s health. The drawbacks of conventional treatments necessitate the development of alternative strategies, where gene therapy has regained hope in achieving an efficient eradication of aggressive tumors. Monocarboxylate transporter 4 (MCT4) plays pivotal roles in the growth and survival of various tumors, which offers a promising target for treatment. In the present study, pH-responsive lipid nanoparticles (LNPs) based on the ionizable lipid,1,2-dioleoyl-3-dimethylammonium propane (DODAP), were designed for the delivery of siRNA targeting MCT4 gene to the breast cancer cells. Following multiple steps of characterization and optimization, the anticancer activities of the LNPs were assessed against an aggressive breast cancer cell line, 4T1, in comparison with a normal cell line, LX-2. The selection of the helper phospholipid to be incorporated into the LNPs had a dramatic impact on their gene delivery performance. The optimized LNPs enabled a powerful MCT4 silencing by ∼90 % at low siRNA concentrations, with a subsequent ∼80 % cytotoxicity to 4T1 cells. Meanwhile, the LNPs demonstrated a 5-fold higher affinity to the breast cancer cells versus the normal cells, in which they had a minimum effect. Moreover, the MCT4 knockdown by the treatment remodeled the cytokine profile in 4T1 cells, as evidenced by 90 % and ∼64 % reduction in the levels of TNF-α and IL-6; respectively. The findings of this study are promising for potential clinical applications. Furthermore, the simple and scalable delivery vector developed herein can serve as a breast cancer-targeting platform for the delivery of other RNA therapeutics.

Background: A fracture is considered a medical emergency leading to considerable complications. Aim: This study aimed to describe the accelerating action of Ag-NPs-FG on fracture healing in rabbits. Methods: Silver NPs (AgNPs) were reduced with fenugreek (FG), loaded into a starch gel base, and investigated for their morphology, size, and charge. Four equal groups were randomly formed of 40 adult male rabbits. A 3.5 mm diameter bone defect was created at the proximal metaphysis of the right tibia in each rabbit. Groups 1–4 were injected with placebo saline, AgNPs-FG, plain gel, and FG-gel at the bone defect zone, respectively. The healing was assessed for 8 weeks postoperatively based on the radiographic, bone turnover markers, and histopathological examinations. Results: The AgNPs-FG was obtained as a faint reddish color, spherical in shape, with an absorbance of 423 nm, a size of 118.0 ± 1.7 nm, and a surface charge of −7.8 ± 0.518 mV. The prepared AgNPs-FG hydrogel was clear, translucent, and homogenous. The pH values were 6.55–6.5 ± 0.2, the viscosity of 4,000 and 1,875 cPs, and spreadability of 1.6 ± 0.14 and 2.0 ± 0.15 for both FG and AgNPs-FG hydrogel, respectively. The radiographic union scale was significantly (p < 0.05) improved in group 2 with a significant (p < 0.05) increase in bone turnover markers was found in comparison to other treated groups. Histopathological examination revealed the formation of mature bone on the 28th postoperative day in groups 2 and 4. Conclusion: Colloidal nano-formulation of AgNPs-FG loaded hydrogel could be a promising formulation to accelerate rabbits’ tibial bone healing process.

Wound healing is a critical process essential for the body’s recovery from injuries, often complicated by bacterial infections. Silver nanoparticles (AgNPs) have gained attention due to their antibacterial and tissue-regenerative properties. However, conventional chemical synthesis methods for AgNPs pose environmental risks. This study utilizes Ziziphus spina-christi (ZSC) extract for the eco-friendly synthesis of AgNPs, evaluating their antibacterial and wound-healing capabilities. The AgNPs-ZSC showed an absorption maximum at λ max of 460 nm, a particle size of 111.2 ± 1.09 nm, a polydispersity index of 0.38 ± 0.006, and a zeta potential of −27.0 ± 0.231 mV. The synthesized AgNPs-ZSC were spherical, non-aggregated, and exhibited potent antibacterial activity superior to chloramphenicol. Furthermore, the AgNPs-ZSC cream significantly promoted wound closure, epithelial tissue proliferation, and granulation tissue formation in rats, showing no signs of toxicity or adverse reactions. In conclusion, AgNPs-ZSC cream demonstrates excellent antibacterial and wound-healing properties, presenting a sustainable alternative to conventional chemical methods for AgNP synthesis.

Introduction

Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for targeted smart drug delivery (SDD) of pharmaceuticals, improving the precision of tumor cell targeting in therapy.

Significance

Magnetic hyperthermia (MHT) treatment using magneto-liposomes (MLs) has emerged as a promising adjuvant cancer therapy.

Methods

CoFe₂O₄ magnetic NPs (MNPs) were conjugated with nanoliposomes to form MLs, and the anticancer drug quercetin (Que) was loaded into MLs, forming Que-MLs composites for antitumor approach. The aim was to prepare Que-MLs for DD systems (DDS) under an alternating magnetic field (AMF), termed chemotherapy/hyperthermia (chemo-HT) techniques. The encapsulation efficiency (EE), drug loading capacity (DL), and drug release (DR) of Que and Que-MLs were evaluated.

Results

The results confirmed successful Que-loading on the surface of MLs, with an average diameter of 38 nm and efficient encapsulation into MLs (69%). In vitro, experimental results on MCF-7 breast cells using MHT showed high cytotoxic effects of novel Que-MLs on MCF-7 cells. Various analyses, including cytotoxicity, apoptosis, cell migration, western blotting, fluorescence imaging, and cell membrane internalization, were conducted. The Acridine Orange-ethidium bromide double fluorescence test identified 35% early and 55% late apoptosis resulting from Que-MLs under the chemo-HT group. TEM results indicated MCF-7 cell membrane internalization and digestion of Que-MLs, suggesting the presence of early endosome-like vesicles on the cytoplasmic periphery.

Conclusions

Que-MLs exhibited multi-modal chemo-HT effects, displaying high toxicity against MCF-7 BC cells and showing promise as a potent cytotoxic agent for BC chemotherapy.

Introduction: Cancers are regarded as hazardous due to their high worldwide death rate, with breast cancer (BC), which affects practically all cancer patients globally, playing a significant role in this statistic. The therapeutic approach for BC has not advanced using standard techniques, such as specialized naringin (NG) chemotherapy. Instead, a novel strategy has been utilized to enhance smart drug delivery (SDD) to tumors.

Significance: Herein, we established NG-loaded zinc metal-organic framework-5 (NG-MOF-5) coated with liponiosomes (LNs) to manufacture NG-MOF-5@LNs nanoparticles (NPs) for antibacterial and cancer treatment.

Methods: MOF-5, NG, and NG-MOF-5@LNs were evaluated with XRD, thermogravimetric analysis (TGA), FTIR, SEM, TEM, PDI, ZP, encapsulation efficiency (EE), loading efficiency (LE), and drug release (DR) kinetics. We examined the antibacterial activity involving minimum inhibitory concentration (MIC) and zone of inhibition by NG, MOF-5, and NG-MOF-5@LNs. The cell viability, necrosis, and total apoptosis (late and early) were evaluated for anti-cancer activity against MCF-7 BC cells.

Results: TEM results demonstrated that NG-MOF-5@LNs formed monodispersed spherical-like particles with a size of 122.5 nm, PDI of 0.139, and ZP of +21 mV. The anti-microbial activity results indicated that NG-MOF-5@LNs exhibited potent antibacterial effects, as evidenced by inhibition zones and MIC values. The Higuchi model indicates an excellent fit (R² = 0.9988). The MTT assay revealed anti-tumor activity against MCF-7 BC cells, with IC₅₀ of 21 µg/mL for NG-MOF-5@LNs and demonstrating a total apoptosis effect of 68.2% on MCF-7 cells.

Conclusion: NG-MOF-5@LNs is anticipated to show as an effective antimicrobial and novel long-term-release antitumor agent and might be more suitable for MCF-7 cell therapy.