Breast Cancer Inhibition by Biosynthesized Titanium Dioxide Nanoparticles Is Comparable to Free Doxorubicin but Appeared Safer in BALB/c Mice

Abstract

Cancer remains a global health burden prompting affordable, target-oriented, and safe chemotherapeutic agents to reduce its incidence rate worldwide. In this study, a rapid, cost-effective, and green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) has been carried out; Ex vivo and in vivo evaluation of their safety and anti-tumor efficacy compared to doxorubicin (DOX), a highly efficient breast anti-cancer agent but limited by severe cardiotoxicity in many patients. Thereby, TiO2 NPs were eco-friendly synthetized using aqueous leaf extract of the tropical medicinal shrub Zanthoxylum armatum as a reducing agent. Butanol was used as a unique template. TiO2 NPs were physically characterized by ultraviolet-visible (UV–Vis) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscope (SEM), X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) as routine state-of-the art techniques. The synthesized TiO2 NPs were then evaluated for their cytotoxicity (by MTT, FACS, and oxidative stress assays) in 4T1 breast tumor cells, and their hemocompatibility (by hemolysis assay). In vivo anti-tumor efficacy and safety of the TiO2 NPs were further assessed using subcutaneous 4T1 breast BALB/c mouse tumor model. The greenly prepared TiO2 NPs were small, spherical, and crystalline in nature. Interestingly, they were hemocompatible and elicited a strong DOX-like concentration-dependent cytotoxicity-induced apoptosis both ex vivo and in vivo (with a noticeable tumor volume reduction). The underlying molecular mechanism was, at least partially, mediated through reactive oxygen species (ROS) generation (lipid peroxidation). Unlike DOX (P < 0.05), it is important to mention that no cardiotoxicity or altered body weight were observed in both the TiO2 NPs-treated tumor-bearing mouse group and the PBS-treated mouse group (P > 0.05). Taken together, Z. armatum-derived TiO2 NPs are cost-effective, more efficient, and safer than DOX. The present findings shall prompt clinical trials using green TiO2 NPs, at least as a possible alternative modality to DOX for effective breast cancer therapy.

Assessment of a Coated Mitomycin-Releasing Biodegradable Ureteral Stent as an Adjuvant Therapy in Upper Urothelial Carcinoma: A Comparative In Vitro Study

“…On the other hand, in a study assessing a very promising compound, such as Titanium dioxide nanoparticles to inhibit tumor development, which has shown in cell culture and in animal models similar results to current chemotherapy (Doxorubicin) but which reduces the side effects associated with conventional therapies. The researchers find, as in our study, that exposure at 6 and 12 h reach their maximal uptake and relate this to anti-tumor efficacy [ 34 ]. Regarding this MMC release rate, we found a huge difference between the two formulations, especially at 12 h, with a significantly higher concentration of MMC released by the BraidStent-SF-MMC2 group ( Table 1 ).…”

Development of nanocubosomes co-loaded with dual anticancer agents curcumin and temozolomide for effective colon cancer therapy

“…The presence of representative functional groups and intramolecular interactions amid the drugs and GMO in fabricated nanocubosomes were analyzed by FTIR spectroscopy (Bruker, Karlsruhe, Germany) (Iqbal et al., 2021 ; Khan et al., 2022 ). Briefly, a small quantity of Cur, TMZ, CTNCs and blank nanocubosomes freeze-dried powder were directly placed on sample chamber and IR spectrum was measured in the IR range (500–4000 cm −1 ), with 2 mm sec −1 scanning speed for 120 scans with 4 cm −1 resolution.…”

“…The cell uptake of CTNCs were evaluated in HCT-116 colon cancer cell using our previously reported protocol with minor modifications (H. Iqbal et al., 2021 ). Briefly, HCT-116 cells were seeded at a cell density of 1 × 10 5 cells/well in 1.0 mL complete RPMI-1640 with 10% FCS.…”

Inhibition of Lipid Accumulation and Adipokine Levels in Maturing Adipocytes by Bauhinia rufescens (Lam.) Stem Bark Extract Loaded Titanium Oxide Nanoparticles

“…The green synthesis of nanoparticles (NPs) is majorly preferred and depends on the biological reduction of metal ions by plants, bacteria, etc., to yield NPs with a uniform shape, size, and higher stability [ 4 ]. Metal oxide nanostructures or nanoparticles have been consecutively fabricated, evaluated, and used in commercial and medical applications for two decades [ 5 ].…”

“…Among prominent NPs with demonstrations, both in vitro and in vivo, titanium oxide nanoparticles (TiO 2 -NPs) show unique surface chemistry and morphologies (e.g., sizes and shapes). They display good biocompatibility and exert inherent biological activities (e.g., efficient antimicrobial and antitumor properties) with weak side effects and low eco-toxicity [ 4 ]. Moreover, TiO 2 -NPs prepared using Moringa oleifera leaves were found to possess a potential wound healing activity [ 14 ].…”