International Journal of Molecular Sciences

Research

Jump to: Review

11 pages, 1178 KiB

Open AccessArticle

Enhanced Cytotoxicity and Receptor Modulation by SMA-WIN 55,212-2 Micelles in Glioblastoma Cells

by Safa Taha, Muna Aljishi, Ameera Sultan, Kannan Sridharan, Sebastien Taurin, Khaled Greish and Moiz Bakhiet

Int. J. Mol. Sci. 2025, 26(10), 4544; https://doi.org/10.3390/ijms26104544 - 9 May 2025

Abstract

Glioblastoma (GBM), a devastating brain malignancy, resists conventional therapies due to molecular heterogeneity and the blood–brain barrier’s significant restriction on drug delivery. Cannabinoids like WIN 55,212-2 show promise but are limited by poor solubility and systemic toxicity. To address these challenges, we evaluated [...] Read more.

Glioblastoma (GBM), a devastating brain malignancy, resists conventional therapies due to molecular heterogeneity and the blood–brain barrier’s significant restriction on drug delivery. Cannabinoids like WIN 55,212-2 show promise but are limited by poor solubility and systemic toxicity. To address these challenges, we evaluated styrene–maleic acid (SMA) micellar encapsulation of WIN 55,212-2 (SMA-WIN) against free WIN in epithelial (LN18) and mesenchymal (A172) GBM cell lines, targeting cytotoxicity and receptor modulation (CB1, CB2, TRPV1, PPAR-γ). SMA-WIN exhibited significantly enhanced cytotoxicity, achieving IC50 values of 12.48 µM (LN18) and 16.72 µM (A172) compared to 20.97 µM and 30.9 µM for free WIN, suggesting improved cellular uptake via micellar delivery. In LN18 cells, both formulations upregulated CB1 and CB2, promoting apoptosis. Notably, SMA-WIN uniquely increased PPAR-γ expression by 2.3-fold in A172 cells, revealing a mesenchymal-specific mechanism absent in free WIN, which primarily modulated CB1/CB2. These findings position SMA-WIN as a promising candidate for precision GBM therapy, particularly for resistant mesenchymal subtypes, paving the way for in vivo validation to confirm blood–brain barrier penetration and clinical translation. Full article

(This article belongs to the Special Issue Toxicity of Nanoparticles)

► Show Figures

Figure 1

19 pages, 1892 KiB

Open AccessArticle

Prometastatic Potential of Non-Functionalized Multiwalled Carbon Nanotubes in the MDA-MB-436 Breast Cancer Cell Line Model

by Magdalena Matysiak-Kucharek, Krzysztof Sawicki, Marcin Kruszewski, Jacek Kurzepa and Lucyna Kapka-Skrzypczak

Int. J. Mol. Sci. 2025, 26(6), 2777; https://doi.org/10.3390/ijms26062777 - 19 Mar 2025

Cited by 1 | Viewed by 326

Abstract

Multiwalled carbon nanotubes (MWCNTs) are used in many areas of industry and medicine. However, there is evidence suggesting profibrogenic action of MWCNTs, probably via the epithelial–mesenchymal transition mechanism (EMT). The aim of this study was to evaluate the prometastatic activity of 5–20 nm [...] Read more.

Multiwalled carbon nanotubes (MWCNTs) are used in many areas of industry and medicine. However, there is evidence suggesting profibrogenic action of MWCNTs, probably via the epithelial–mesenchymal transition mechanism (EMT). The aim of this study was to evaluate the prometastatic activity of 5–20 nm and 50–80 nm MWCNTs against cells of the MDA-MB-436 line. We used MTT and NR assays to determine MWCNTs’ cytotoxicity and the level of malonylodialdehyde and thiol compounds as indicators of oxidative stress. qRT-PCR was used to examine the expression of EMT markers. The QCM Chemotaxis Cell Migration Assay was used to assess cell migration, while the Cytokine Array Kit and Apoptosis Array Kit were used to determine cytokine expression and induction of apoptosis. The interleukin 6, C-X-C motif chemokine ligand 8, and tumor growth factor beta 1 (TGFB1) secretion was determined by ELISA. MWCNTs were toxic to MDA-MB-436 cells and induced cell death via the apoptosis pathway. MWCNTs induced a low level of oxidative stress and were associated with increased secretion of pro-inflammatory cytokines and chemokines, including proteins important in breast cancer metastasis. Cells incubated with MWCNTs showed increased expression of mesenchymal EMT markers. However, in contrast to these results, the migration of MWCNT-treated cells increased only modestly relative to untreated cells. Also, the secretion of TGFB1, a key inducer and regulator of EMT, increased only slightly. In summary, the multifaceted effect of MWCNTs on cancer cells encourages further work on the safety of nanomaterials. Full article

(This article belongs to the Special Issue Toxicity of Nanoparticles)

► Show Figures

Figure 1

20 pages, 1958 KiB

Open AccessArticle

Assessing the Toxicity of Metal- and Carbon-Based Nanomaterials In Vitro: Impact on Respiratory, Intestinal, Skin, and Immune Cell Lines

by Juliana Carrillo-Romero, Gartze Mentxaka, Adrián García-Salvador, Alberto Katsumiti, Susana Carregal-Romero and Felipe Goñi-de-Cerio

Int. J. Mol. Sci. 2024, 25(20), 10910; https://doi.org/10.3390/ijms252010910 - 10 Oct 2024

Cited by 6 | Viewed by 1936

Abstract

The field of nanotechnology has experienced exponential growth, with the unique properties of nanomaterials (NMs) being employed to enhance a wide range of products across diverse industrial sectors. This study examines the toxicity of metal- and carbon-based NMs, with a particular focus on [...] Read more.

The field of nanotechnology has experienced exponential growth, with the unique properties of nanomaterials (NMs) being employed to enhance a wide range of products across diverse industrial sectors. This study examines the toxicity of metal- and carbon-based NMs, with a particular focus on titanium dioxide (TiO₂), zinc oxide (ZnO), silica (SiO₂), cerium oxide (CeO₂), silver (Ag), and multi-walled carbon nanotubes (MWCNTs). The potential health risks associated with increased human exposure to these NMs and their effect on the respiratory, gastrointestinal, dermal, and immune systems were evaluated using in vitro assays. Physicochemical characterisation of the NMs was carried out, and in vitro assays were performed to assess the cytotoxicity, genotoxicity, reactive oxygen species (ROS) production, apoptosis/necrosis, and inflammation in cell lines representative of the systems evaluated (3T3, Caco-2, HepG2, A549, and THP-1 cell lines). The results obtained show that 3T3 and A549 cells exhibit high cytotoxicity and ROS production after exposure to ZnO NMs. Caco-2 and HepG2 cell lines show cytotoxicity when exposed to ZnO and Ag NMs and oxidative stress induced by SiO₂ and MWCNTs. THP-1 cell line shows increased cytotoxicity and a pro-inflammatory response upon exposure to SiO₂. This study emphasises the importance of conducting comprehensive toxicological assessments of NMs given their physicochemical interactions with biological systems. Therefore, it is of key importance to develop robust and specific methodologies for the assessment of their potential health risks. Full article

(This article belongs to the Special Issue Toxicity of Nanoparticles)

► Show Figures

Figure 1

19 pages, 4350 KiB

Open AccessArticle

Characterization of Stealth Liposome-Based Nanoparticles Encapsulating the ACAT1/SOAT1 Inhibitor F26: Efficacy and Toxicity Studies In Vitro and in Wild-Type Mice

by Junghoon Lee, Adrianna L. De La Torre, Felix L. Rawlinson, Dylan B. Ness, Lionel D. Lewis, William F. Hickey, Catherine C. Y. Chang and Ta Yuan Chang

Int. J. Mol. Sci. 2024, 25(17), 9151; https://doi.org/10.3390/ijms25179151 - 23 Aug 2024

Cited by 1 | Viewed by 1385

Abstract

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme responsible for catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and [...] Read more.

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme responsible for catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high-affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer’s disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG₂₀₀₀/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26’s efficacy and toxicity compared to F12511. The results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs), and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD. Full article

(This article belongs to the Special Issue Toxicity of Nanoparticles)

► Show Figures

Figure 1

19 pages, 6338 KiB

Open AccessArticle

Cytotoxicity and Genotoxicity Effects of a Magnetic Zeolite Composite in Daphnia magna (Straus, 1820)

by Jacquelyne Y. Zarria-Romero and Juan A. Ramos-Guivar

Int. J. Mol. Sci. 2024, 25(14), 7542; https://doi.org/10.3390/ijms25147542 - 9 Jul 2024

Cited by 2 | Viewed by 1148

Abstract

Zeolite type 5A combined with the magnetic properties of maghemite nanoparticles facilitate the rapid absorption of heavy metals, which makes them an interesting proposal for the remediation of water contaminated with lead and arsenic. However, the physicochemical analysis related to concentration and size [...] Read more.

Zeolite type 5A combined with the magnetic properties of maghemite nanoparticles facilitate the rapid absorption of heavy metals, which makes them an interesting proposal for the remediation of water contaminated with lead and arsenic. However, the physicochemical analysis related to concentration and size for the use of this magnetic zeolite composite (MZ0) in water bodies and the possible toxicological effects on aquatic fauna has not yet been carried out. The main objective of the research work is to determine lethal concentrations that cause damage to Daphnia magna based on LC₅₀ tests, morphology, reproductive rate, and quantification of the expression of three genes closely involved in the morphological development of vital structures (Glass, NinaE, Pph13). To achieve this objective, populations of neonates and young individuals were used, and results showed that the LC₅₀ for neonates was 11,314 mg L⁻¹, while for young individuals, it was 0.0310 mg L⁻¹. Damage to morphological development was evidenced by a decrease in eye size in neonates, an increase in eye size in young individuals, variations in the size of the caudal spine for both age groups, and slight increases in the heart size, body, and antenna for both age groups. The reproductive rate of neonates was not affected by the lower concentrations of MZ0, while in young individuals, the reproductive rate decreased by more than 50% from the minimum exposure concentration of MZ0. And for both ages, Glass gene expression levels decreased as the MZ0 concentration increased. Also, the MZ0 evidenced its affinity for the exoskeleton of D. magna, which was observed using both light microscopy and electron microscopy. It is concluded that MZ0 did not generate significant damage in the mortality, morphology, reproductive rate, or gene expression in D. magna at lower concentrations, demonstrating the importance of evaluating the possible impacts on different life stages of the cladoceran. Full article

(This article belongs to the Special Issue Toxicity of Nanoparticles)

► Show Figures

Figure 1

Review

Jump to: Research

34 pages, 2139 KiB

Open AccessReview

Comprehensive Analysis of the Potential Toxicity of Magnetic Iron Oxide Nanoparticles for Medical Applications: Cellular Mechanisms and Systemic Effects

by Julia Nowak-Jary and Beata Machnicka

Int. J. Mol. Sci. 2024, 25(22), 12013; https://doi.org/10.3390/ijms252212013 - 8 Nov 2024

Cited by 6 | Viewed by 1849

Abstract

Owing to recent advancements in nanotechnology, magnetic iron oxide nanoparticles (MNPs), particularly magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃), are currently widely employed in the field of medicine. These MNPs, characterized by their large specific surface area, [...] Read more.

Owing to recent advancements in nanotechnology, magnetic iron oxide nanoparticles (MNPs), particularly magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃), are currently widely employed in the field of medicine. These MNPs, characterized by their large specific surface area, potential for diverse functionalization, and magnetic properties, have found application in various medical domains, including tumor imaging (MRI), radiolabelling, internal radiotherapy, hyperthermia, gene therapy, drug delivery, and theranostics. However, ensuring the non-toxicity of MNPs when employed in medical practices is paramount. Thus, ongoing research endeavors are essential to comprehensively understand and address potential toxicological implications associated with their usage. This review aims to present the latest research and findings on assessing the potential toxicity of magnetic nanoparticles. It meticulously delineates the primary mechanisms of MNP toxicity at the cellular level, encompassing oxidative stress, genotoxic effects, disruption of the cytoskeleton, cell membrane perturbation, alterations in the cell cycle, dysregulation of gene expression, inflammatory response, disturbance in ion homeostasis, and interference with cell migration and mobility. Furthermore, the review expounds upon the potential impact of MNPs on various organs and systems, including the brain and nervous system, heart and circulatory system, liver, spleen, lymph nodes, skin, urinary, and reproductive systems. Full article

(This article belongs to the Special Issue Toxicity of Nanoparticles)

► Show Figures

Figure 1

20 pages, 5190 KiB

Open AccessReview

Mapping Microplastics in Humans: Analysis of Polymer Types, and Shapes in Food and Drinking Water—A Systematic Review

by Alena Vdovchenko and Marina Resmini

Int. J. Mol. Sci. 2024, 25(13), 7074; https://doi.org/10.3390/ijms25137074 - 27 Jun 2024

Cited by 7 | Viewed by 3944

Abstract

Microplastics (MPs) pervade the environment, infiltrating food sources and human bodies, raising concerns about their impact on human health. This review is focused on three key questions: (i) What type of polymers are humans most exposed to? (ii) What are the prevalent shapes [...] Read more.

Microplastics (MPs) pervade the environment, infiltrating food sources and human bodies, raising concerns about their impact on human health. This review is focused on three key questions: (i) What type of polymers are humans most exposed to? (ii) What are the prevalent shapes of MPs found in food and human samples? (iii) Are the data influenced by the detection limit on the size of particles? Through a systematic literature analysis, we have explored data on polymer types and shapes found in food and human samples. The data provide evidence that polyester is the most commonly detected polymer in humans, followed by polyamide, polyurethane, polypropylene, and polyacrylate. Fibres emerge as the predominant shape across all categories, suggesting potential environmental contamination from the textile industry. Studies in humans and drinking water reported data on small particles, in contrast to larger size MPs detected in environmental research, in particular seafood. Discrepancies in size detection methodologies across different reports were identified, which could impact some of the discussed trends. This study highlights the need for more comprehensive research on the interactions between MPs and biological systems and the effects of MPs on toxicity, together with standardised analytical methodologies to accurately assess contamination levels and human exposure. Understanding these dynamics is essential for formulating effective strategies to mitigate the environmental and health implications of MP pollution. Full article

(This article belongs to the Special Issue Toxicity of Nanoparticles)

► Show Figures

Figure 1

40 pages, 1445 KiB

Open AccessReview

Gold Nanoparticles (AuNPs)—Toxicity, Safety and Green Synthesis: A Critical Review

by Łukasz Niżnik, Maciej Noga, Damian Kobylarz, Adrian Frydrych, Alicja Krośniak, Lucyna Kapka-Skrzypczak and Kamil Jurowski

Int. J. Mol. Sci. 2024, 25(7), 4057; https://doi.org/10.3390/ijms25074057 - 5 Apr 2024

Cited by 55 | Viewed by 7748

Abstract

In recent years, the extensive exploration of Gold Nanoparticles (AuNPs) has captivated the scientific community due to their versatile applications across various industries. With sizes typically ranging from 1 to 100 nm, AuNPs have emerged as promising entities for innovative technologies. This article [...] Read more.

In recent years, the extensive exploration of Gold Nanoparticles (AuNPs) has captivated the scientific community due to their versatile applications across various industries. With sizes typically ranging from 1 to 100 nm, AuNPs have emerged as promising entities for innovative technologies. This article comprehensively reviews recent advancements in AuNPs research, encompassing synthesis methodologies, diverse applications, and crucial insights into their toxicological profiles. Synthesis techniques for AuNPs span physical, chemical, and biological routes, focusing on eco-friendly “green synthesis” approaches. A critical examination of physical and chemical methods reveals their limitations, including high costs and the potential toxicity associated with using chemicals. Moreover, this article investigates the biosafety implications of AuNPs, shedding light on their potential toxic effects on cellular, tissue, and organ levels. By synthesizing key findings, this review underscores the pressing need for a thorough understanding of AuNPs toxicities, providing essential insights for safety assessment and advancing green toxicology principles. Full article

(This article belongs to the Special Issue Toxicity of Nanoparticles)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Toxicity of Nanoparticles

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI