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Breast cancer remains a global health challenge, prompting interest in the anticancer properties of other drugs, including chlorpromazine (CPZ). This study presents a novel approach in breast cancer treatment using laser irradiated CPZ. CPZ dissolved in distilled water, was exposed to 266 nm laser irradiation for varying durations, characterized by UV-Vis and FTIR spectroscopy, followed by drug-likeness and ADME-Tox predictions. In vitro assays evaluated the cytotoxicity and cellular effects on MCF-7 breast cancer cells, and compared with MCF-12 A healthy cell line. Laser irradiation altered CPZ molecular structure resulting in photoproducts with favourable drug-like properties and ADME-Tox profiles. In vitro evaluations demonstrate dose and irradiation time-dependent cytotoxicity against breast cancer cells, and reduced toxicity on healthy cell line. Significant alterations in F-actin organization, and excessive ROS generation were also proved, suggesting the potential of laser-modified CPZ for breast cancer therapy. This study introduces a novel approach to breast cancer treatment through laser irradiated CPZ, highlighting promising advancements in therapy and emphasizing the role of laser-generated compounds. [ABSTRACT FROM AUTHOR]

The type of experimental model for the in vitro testing of drug formulations efficiency represents an important tool in cancer biology, with great attention being granted to three-dimensional (3D) cultures as these offer a closer approximation of the clinical sensitivity of drugs. In this study, the effects induced by carboxyl-functionalized single-walled carbon nanotubes complexed with cisplatin (SWCNT–COOH–CDDP) and free components (SWCNT–COOH and CDDP) were compared between conventional 2D- and 3D-spheroid cultures of human breast cancer cells. The 2D and 3D breast cancer cultures were exposed to various doses of SWCNT–COOH (0.25–2 μg/mL), CDDP (0.158–1.26 μg/mL) and the same doses of SWNCT–COOH–CDDP complex for 24 and 48 h. The anti-tumor activity, including modulation of cell viability, oxidative stress, proliferation, apoptosis, and invasion potential, was explored by spectrophotometric and fluorometric methods, immunoblotting, optical and fluorescence microscopy. The SWCNT–COOH–CDDP complex proved to have high anti-cancer efficiency on 2D and 3D cultures by inhibiting cell proliferation and activating cell death. A dose of 0.632 μg/mL complex triggered different pathways of apoptosis in 2D and 3D cultures, by intrinsic, extrinsic, and reticulum endoplasmic pathways. Overall, the 2D cultures showed higher susceptibility to the action of complex compared to 3D cultures and SWCNT–COOH–CDDP proved enhanced anti-tumoral activity compared to free CDDP. [ABSTRACT FROM AUTHOR]

In this study, we report on the development of hydroxyapatite (HAp) and samarium-doped hydroxyapatite (SmHAp) nanoparticles using a cost-effective method and their biological effects on a bone-derived cell line MC3T3-E1. The physicochemical and biological features of HAp and SmHAp nanoparticles are explored. The X-ray diffraction (XRD) studies revealed that no additional peaks were observed after the integration of samarium (Sm) ions into the HAp structure. Valuable information regarding the molecular structure and morphological features of nanoparticles were obtained by using Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The elemental composition obtained by using energy-dispersive X-ray spectroscopy (EDS) confirmed the presence of the HAp constituent elements, Ca, O, and P, as well as the presence and uniform distribution of Sm3+ ions. Both HAp and SmHAp nanoparticles demonstrated biocompatibility at concentrations below 25 μg/mL and 50 μg/mL, respectively, for up to 72 h of exposure. Cell membrane integrity was preserved following treatment with concentrations up to 100 μg/mL HAp and 400 μg/mL SmHAp, confirming the role of Sm3+ ions in enhancing the cytocompatibility of HAp. Furthermore, our findings reveal a positive, albeit limited, effect of SmHAp nanoparticles on the actin dynamics, osteogenesis, and cell migration compared to HAp nanoparticles. Importantly, the biological results highlight the potential role of Sm3+ ions in maintaining cellular balance by mitigating disruptions in Ca2+ homeostasis induced by HAp nanoparticles. Therefore, our study represents a significant contribution to the safety assessment of both HAp and SmHAp nanoparticles for biomedical applications focused on bone regeneration. [ABSTRACT FROM AUTHOR]

Curcumin is a polyphenol of the Curcuma longa plant, which can be used for various medicinal purposes, such as inflammation and cancer treatment. In this context, two symmetric curcumin derivatives (D1—(1E,6E)-1,7-bis(4-acetamidophenyl)hepta-1,6-diene-3,5-dione and D2—p,p-dihydroxy di-cinnamoyl methane) were obtained by the microwave-based method and evaluated for their antitumoral effect on human cervix cancer in comparison with toxicity on non-tumoral cells, taking into account that they were predicted to act as apoptosis agonists or anti-inflammatory agents. The HeLa cell line was incubated for 24 and 72 h with a concentration of 50 μg/mL of derivatives that killed almost half of the cells compared to the control. In contrast, these compounds did not alter the viability of MRC-5 non-tumoral lung fibroblasts until 72 h of incubation. The nitric oxide level released by HeLa cells was higher compared to MRC-5 fibroblasts after the incubation with 100 μg/mL. Both derivatives induced the decrease of catalase activity and glutathione levels in cancer cells without targeting the same effect in non-tumoral cells. Furthermore, the Western blot showed an increased protein expression of HSP70 and a decreased expression of HSP60 and MCM2 in cells incubated with D2 compared to control cells. We noticed differences regarding the intensity of cell death between the tested derivatives, suggesting that the modified structure after synthesis can modulate their function, the most prominent effect being observed for sample D2. In conclusion, the outcomes of our in vitro study revealed that these microwave-engineered curcumin derivatives targeted tumor cells, much more specifically, inducing their death. [ABSTRACT FROM AUTHOR]

The channels from the superfamily of transient receptor potential (TRP) activated by reactive oxygen species (ROS) can be defined as redox channels. Those with the best exposure of the cysteine residues and, hence, the most sensitive to oxidative stress are TRPC4, TRPC5, TRPV1, TRPV4, and TRPA1, while others, such as TRPC3, TRPM2, and TRPM7, are indirectly activated by ROS. Furthermore, activation by ROS has different effects on the tumorigenic process: some TRP channels may, upon activation, stimulate proliferation, apoptosis, or migration of cancer cells, while others inhibit these processes, depending on the cancer type, tumoral microenvironment, and, finally, on the methods used for evaluation. Therefore, using these polymodal proteins as therapeutic targets is still an unmet need, despite their draggability and modulation by simple and mostly unharmful compounds. This review intended to create some cellular models of the interaction between oxidative stress, TRP channels, and inflammation. Although somewhat crosstalk between the three actors was rather theoretical, we intended to gather the recently published data and proposed pathways of cancer inhibition using modulators of TRP proteins, hoping that the experimental data corroborated clinical information may finally bring the results from the bench to the bedside. [ABSTRACT FROM AUTHOR]

This study aims to design and test different formulations composed of dextran-coated iron oxide nanoparticles (IONPs) loaded with 5-Fluorouracil (5-FU) with varying nanoparticle:drug ratios on colorectal cancer cells. The stable suspension of IONPs s was synthesized by the adapted co-precipitation method. The stable suspension of IONPs was mixed with a solution of dextran and 5-FU solubilized in a saline solution. The final suspensions with optimized ratios of IONP:5-FU in the final suspension were 0.5:1, 1:1, and 1.5:1. The information on the morphology and size distribution of the IONPs suspension and IONP loads with 5-FU was obtained using scanning electron microscopy (SEM). The presence of 5-FU and dextran on the surface of the IONPs was highlighted by energy-dispersive X-ray spectroscopy (EDS) studies. The determination of the surface charge of the nanoparticles in the final suspensions of IONP:5-FU was achieved by measuring the zeta potential (ζ). The hydrodynamic diameter of the resulting suspensions of IONP:5-FU was determined by dynamic light scattering (DLS). A cytocompatibility analysis was performed using Caco-2 (human epithelial colorectal adenocarcinoma) cells. In this research, our goal was to find a relationship between the formulation ratio of nanoparticles and drug, and the cellular response after exposure, as a strategy to increase the efficacy of this drug-delivery system. The nanoparticle uptake and antitumor activity, including modulation of oxidative stress, apoptosis, and proliferation biomarkers, were analyzed. The present study showed that the nanoformulation with the ratio IONP:5-FU 1.5:1 had the highest anti-tumor efficiency. Moreover, decreased MCM-2 expression in Caco-2 cells exposed to dextran-coated iron oxide nanoparticles loaded with 5-FU was demonstrated for the first time. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the biological response induced by hydroxyapatite (HAp) and zinc-doped HAp (ZnHAp) in human gingival fibroblasts and to explore their antimicrobial activity. The ZnHAp (with xZn = 0.00 and 0.07) powders, synthesized by the sol-gel method, retained the crystallographic structure of pure HA without any modification. Elemental mapping confirmed the uniform dispersion of zinc ions in the HAp lattice. The size of crystallites was 18.67 ± 2 nm for ZnHAp and 21.54 ± 1 nm for HAp. The average particle size was 19.38 ± 1 nm for ZnHAp and 22.47 ± 1 nm for HAp. Antimicrobial studies indicated an inhibition of bacterial adherence to the inert substrate. In vitro biocompatibility was tested on various doses of HAp and ZnHAp after 24 and 72 h of exposure and revealed that cell viability decreased after 72 h starting with a dose of 31.25 µg/mL. However, cells retained membrane integrity and no inflammatory response was induced. High doses (such as 125 µg/mL) affected cell adhesion and the architecture of F-actin filaments, while in the presence of lower doses (such as 15.625 µg/mL), no modifications were observed. Cell proliferation was inhibited after treatment with HAp and ZnHAp, except the dose of 15.625 µg/mL ZnHAp at 72 h of exposure, when a slight increase was observed, proving an improvement in ZnHAp activity due to Zn doping. [ABSTRACT FROM AUTHOR]

The combination of TiO2 nanoparticles (NPs) and photosensitizers (PS) may offer significant advantages in photodynamic therapy (PDT) of melanoma, such as improved cell penetration, enhanced ROS production, and cancer selectivity. In this study, we aimed to investigate the photodynamic effect of 5,10,15,20-(Tetra-N-methyl-4-pyridyl)porphyrin tetratosylate (TMPyP4) complexes with TiO2 NPs on human cutaneous melanoma cells by irradiation with 1 mW/cm2 blue light. The porphyrin conjugation with the NPs was analyzed by absorption and FTIR spectroscopy. The morphological characterization of the complexes was performed by Scanning Electron Microscopy and Dynamic Light Scattering. The singlet oxygen generation was analyzed by phosphorescence at 1270 nm. Our predictions indicated that the non-irradiated investigated porphyrin has a low degree of toxicity. The photodynamic activity of the TMPyP4/TiO2 complex was assessed on the human melanoma Mel-Juso cell line and non-tumor skin CCD-1070Sk cell line treated with various concentrations of the PS and subjected to dark conditions and visible light-irradiation. The tested complexes of TiO2 NPs with TMPyP4 presented cytotoxicity only after activation by blue light (405 nm) mediated by the intracellular production of ROS in a dose-dependent manner. The photodynamic effect observed in this evaluation was higher in melanoma cells than the effect observed in the non-tumor cell line, demonstrating a promising potential for cancer-selectivity in PDT of melanoma. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) represent small plastic particles with sizes between 1 μm and 5 mm, are insoluble in water, andclassified as primary (these are originally produced in small sizes) or secondary (the result of the degradation of plastic) types. MPs accumulate in all ecosystems, including freshwater environments, where they are subjected to degradation processes. Due to their ubiquitous nature, freshwater ecosystems, which have a vital importance in human life, are permanently subjected to these small plastic particles. In this context, MPs pollution is considered to be a global issue, and it is associated with toxic effects on all the elements of the freshwater environment. In this review, we present, in detail, the main physical (density, size, color, shape, and crystallinity) and chemical (chemical composition and modification of the MPs' surface) properties of MPs, the mechanism of biodegradation, and the consequences of autotrophic organisms and fauna exposure by focusing on the freshwater environment. The toxicity mechanisms triggered by MPs are related to the critical parameters of the particles: size, concentration, type, and form, but they are also dependent on species exposed to MPs and the exposure route. [ABSTRACT FROM AUTHOR]

Iron-oxide-doped polyaniline (PANI-IO) thin films were obtained by the polymerization of aniline monomers and iron oxide solutions in direct current glow discharge plasma in the absence of a buffer gas for the first time. The PANI-IO thin films were deposited on optical polished Si wafers in order to study surface morphology and evaluate their in vitro biocompatibility. The characterization of the coatings was accomplished using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), metallographic microscopy (MM), and X-ray photoelectron spectroscopy (XPS). In vitro biocompatibility assessments were also conducted on the PANI-IO thin films. It was observed that a uniform distribution of iron oxide particles inside the PANI layers was obtained. The constituent elements of the coatings were uniformly distributed. The Fe-O bonds were associated with magnetite in the XPS studies. The surface morphology of the PANI-IO thin films was assessed by atomic force microscopy (AFM). The AFM topographies revealed that PANI-IO exhibited the morphology of a uniformly distributed and continuous layer. The viability of Caco-2 cells cultured on the Si substrate and PANI-IO coating was not significantly modified compared to control cells. Moreover, after 24 h of incubation, we observed no increase in LDH activity in media in comparison to the control. In addition, our results revealed that the NO levels for the Si substrate and PANI-IO coating were similar to those found in the control sample. [ABSTRACT FROM AUTHOR]

Hanging drop represents a simple approach designed for the generation of 3D models that have potential to be used for the study of solid tumors characteristics. The aim of the study was to develop and characterize the breast cancer 3D cellular models obtained through hanging drop technique using MDA-MB-231 cells. The biological characteristics such as: morphology, cellular viability, proliferation capacity and hypoxia, were monitored for a six-day time period. The morphological evaluation indicated that the 3D models presented the aspect of compact (seeding density of 2500 and 5000 cells/drop) and loose (seeding density of 8000 cells/drop) aggregates, with a decrease in diameter and an increase of their circularity. The cellular viability and proliferation capacity decreased in time and the level of lactate dehydrogenase (LDH) increased in a time-dependent manner, suggesting the presence of necrotic cells that were dispersed in the cellular aggregates. The occurrence of hypoxia process was suggested by the up-regulation of Hsp70 protein expression and increased level of nitric oxide (NO). Moreover, the up-regulation of HIF-1α and poli-ubiquitinated Nrf2 protein expressions and decreased level of reduced glutathione (GSH) indicated the presence of an acute hypoxic environment in MDA-MB-231 3D aggregates. In conclusion, the MDA-MB-231 3D models generated through hanging drop are compact and loose aggregates characterized by an acute hypoxic condition. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticles offer multiple utilization possibilities in biomedicine. In this context, the interaction with cellular structures and their biological effects need to be understood and controlled for clinical safety. New magnetic nanoparticles containing metallic/ carbidic iron and elemental silicon phases were synthesized by laser pyrolysis using Fe(CO)5 vapors and SiH4 gas as Fe and Si precursors, then passivated and coated with biocompatible agents, such as L-3,4-dihydroxyphenylalanine (L-DOPA) and sodium carboxymethyl cellulose (CMC-Na). The resulting magnetic nanoparticles were characterized by XRD, EDS, and TEM techniques. To evaluate their biocompatibility, doses ranging from 0-200 μg/mL hybrid Fe-Si nanoparticles were exposed to Caco2 cells for 24 and 72 h. Doses below 50 μg/mL of both L-DOPA and CMC-Na-coated Fe-Si nanoparticles induced no significant changes of cellular viability or membrane integrity. The cellular internalization of nanoparticles was dependent on their dispersion in culture medium and caused some changes of F-actin filaments organization after 72 h. However, reactive oxygen species were generated after exposure to 25 and 50 μg/mL of both Fe-Si nanoparticles types, inducing the increase of intracellular glutathione level and activation of transcription factor Nrf2. At nanoparticles doses below 50 μg/mL, Caco2 cells were able to counteract the oxidative stress by activating the cellular protection mechanisms. We concluded that in vitro biological responses to coated hybrid Fe-Si nanoparticles depended on particle synthesis conditions, surface coating, doses and incubation time. [ABSTRACT FROM AUTHOR]

PI3K/Akt signaling is one of the most frequently dysregulated pathways in cancer, including triple-negative breast cancer. With considerable roles in tumor growth and proliferation, this pathway is studied as one of the main targets in controlling the therapies' efficiency. Nowadays, the development of nanoparticle–drug conjugates attracts a great deal of attention due to the advantages they provide in cancer treatment. Hence, the main purpose of this study was to design a nanoconjugate based on single-walled carbon nanotubes functionalized with carboxyl groups (SWCNT-COOH) and cisplatin (CDDP) and to explore the potential of inhibiting the PI3K/Akt signaling pathway. MDA-MB-231 cells were exposed to various doses (0.01–2 µg/mL SWCNT-COOH and 0.00632–1.26 µg/mL CDDP) of SWCNT-COOH-CDDP and free components for 24 and 48 h. In vitro biological tests revealed that SWCNT-COOH-CDDP had a high cytotoxic effect, as shown by a time-dependent decrease in cell viability and the presence of a significant number of dead cells in MDA-MB-231 cultures at higher doses. Moreover, the nanoconjugates induced the downregulation of PI3K/Akt signaling, as revealed by the decreased expression of PI3K and p-Akt in parallel with PTEN activation, the promotion of Akt protein degradation, and inhibition of tumor cell migration. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effectiveness in photodynamic therapy of iron oxide nanoparticles (γ-Fe2O3 NPs), synthesized by laser pyrolysis technique, functionalized with 5,10,15,20-(Tetra-4-sulfonatophenyl) porphyrin tetraammonium (TPPS) on human cutaneous melanoma cells, after only 1 min blue light exposure. The efficiency of porphyrin loading on the iron oxide nanocarriers was estimated by using absorption and FTIR spectroscopy. The singlet oxygen yield was determined via transient characteristics of singlet oxygen phosphorescence at 1270 nm both for porphyrin functionalized nanoparticles and rose bengal used as standard. The irradiation was performed with a LED (405 nm, 1 mW/cm2) for 1 min after melanoma cells were treated with TPPS functionalized iron oxide nanoparticles (γ-Fe2O3 NPs_TPPS) and incubated for 24 h. Biological tests revealed a high anticancer effect of γ-Fe2O3 NPs_TPPS complexes indi-cated by the inhibition of tumor cell proliferation, reduction of cell adhesion, and induction of cell death through ROS generated by TPPS under light exposure. The biological assays were combined with the pharmacokinetic prediction of the porphyrin. [ABSTRACT FROM AUTHOR]