Modulatory Effects of Biosynthesized Gold Nanoparticles Conjugated with Curcumin and Paclitaxel on Tumorigenesis and Metastatic Pathways—In Vitro and In Vivo Studies

Abstract

Background: Breast cancer is the most common cancer in women globally, and diagnosing it early and finding potential drug candidates against multi-drug resistant metastatic breast cancers provide the possibilities of better treatment and extending life. Methods: The current study aimed to evaluate the synergistic anti-metastatic activity of Curcumin (Cur) and Paclitaxel (Pacli) individually, the combination of Curcumin–Paclitaxel (CP), and also in conjugation with gold nanoparticles (AuNP–Curcumin (Au-C), AuNP–Paclitaxel (Au-P), and AuNP–Curcumin–Paclitaxel (Au-CP)) in various in vitro and in vivo models. Results: The results from combination treatments of CP and Au-CP demonstrated excellent synergistic cytotoxic effects in triple-negative breast cancer cell lines (MDA MB 231 and 4T1) in in vitro and in vivo mouse models. Detailed mechanistic studies were performed that reveal that the anti-cancer effects were associated with the downregulation of the expression of VEGF, CYCLIN-D1, and STAT-3 genes and upregulation of the apoptotic Caspase-9 gene. The group of mice that received CP combination therapy (with and without gold nanoparticles) showed a significant reduction in the size of tumor when compared to the Pacli alone treatment and control groups. Conclusions: Together, the results suggest that the delivery of gold conjugated Au-CP formulations may help in modulating the outcomes of chemotherapy. The present study is well supported with observations from cell-based assays, molecular and histopathological analyses.

An ICT-guided ratiometric naphthalene–benzothiazole-based probe for the detection of cyanide with real-time applications in human breast cancer cells

“…Results from an in vitro cell cytotoxicity assay (MTT assay) 36,37 showed no substantial toxicity even at a concentration of 100 mM for the ligand MNBTZ (Fig. S2, ESI †).…”

“…2-(1,3-Benzothiazol-2-yl)acetonitrile was prepared according to the reported procedure by Chellappa et al 37 The aldehyde MNA (200 mg, 0.76 mmol), 2-benzothiozoleacetonitrile (132 mg, 0.76 mmol), and piperidine (0.045 g, 0.52 mmol) were dissolved in 10 mL ethanol and the reaction mixture was refluxed for 2 h. A yellow precipitate was formed, which was collected by filtration and washed with cold ethanol. Yield 60.8% (160 mg).…”

“…Yield 76% (380 mg). 2-(1,3-Benzothiazol-2-yl)acetonitrile was prepared according to the reported procedure by Chellappa et al 37 The aldehyde MNA (200 mg, 0.76 mmol), 2-benzothiozoleacetonitrile (132 mg, 0.76 mmol), and piperidine (0.045 g, 0.52 mmol) were dissolved in Scheme 1 Structure of the probe and its sensing of cyanide.…”

A Gold Nanoparticle Bioconjugate Delivery System for Active Targeted Photodynamic Therapy of Cancer and Cancer Stem Cells

“…In a recent study, AuNP nanoparticles were conjugated with curcumin and paclitaxel (Au-CP) to examine its anticancer effect on triple-negative breast cancer cell lines and delineate the signaling genes involved. The report showed considerable inhibition of VEGF, CYCLIN-D1, and STAT-3 signaling genes and high expression of the apoptotic Caspase-9 gene [ 97 ]. Other anticancer agents for actively targeting CSCs signaling pathways are summarized in Table 4 .…”

Effect and mechanism of paclitaxel loaded on magnetic Fe 3 O 4 @mSiO 2 -NH 2 -FA nanocomposites to MCF-7 cells

“…Furthermore, polyoxyethylene castor oil may cause severe allergic reactions, nephrotoxicity, and neurotoxicity when degraded in vivo , posing a great risk to clinical use. Therefore, research on new dosage forms of taxol with high efficiency and low toxicity has been the focus of new drug research in recent years (Suzuki et al., 2022 ; Vemuri et al., 2022 ; Zhang et al., 2022 a).…”