Nanodrugs hold great promise for targeted therapies, but their potential for cytotoxicity remains a major area of concern, threatening both patient safety and clinical translation. In this systematic review, we conducted a systematic investigation of nanotoxicity studies-identified through an AI-assisted screening procedure using Scopus, PubMed, and Elicit AI-to establish the molecular determinants of nanodrug-induced cytotoxicity. Our findings reveal three dominant and linked mechanisms that consistently act in a range of nanomaterials: oxidative stress, inflammatory signaling, and lysosomal disruption. Key nanomaterial properties like chemical structure, size, shape, surface charge, tendency to aggregate, and biocorona formation control these pathways, modulating cellular uptake, reactive oxygen species generation, cytokine release, and subcellular injury. Notably, the most frequent mechanism was oxidative stress, which often initiated downstream inflammatory and apoptotic signaling. By linking these toxicity pathways with particular nanoparticle characteristics, our review presents necessary guidelines for safer, more biocompatible nanodrug formulation design. This extensive framework acknowledges the imperative necessity for mechanistic toxicity assessment in nanopharmaceutical design and underscores the strength of AI tools in driving systematic toxicology studies.

• Klíčová slova
• ROS, cytotoxicity, molecular mechanisms of nanotoxicity, nanodrugs, nanoparticles, oxidative stress,
• MeSH
• apoptóza účinky léků   MeSH
• lidé MeSH
• lyzozomy účinky léků   metabolismus   MeSH
• nanočástice * chemie   toxicita   MeSH
• nanostruktury * toxicita   chemie   MeSH
• oxidační stres účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH
• Názvy látek
• reaktivní formy kyslíku MeSH

DNA nanotechnology has revolutionized materials science and biomedicine by enabling precise manipulation of matter at the nanoscale. DNA nanostructures (DNs) in particular represent a promising frontier for targeted therapeutics. Engineered DNs offer unprecedented molecular programmability, biocompatibility, and structural versatility, making them ideal candidates for advanced drug delivery, organelle regulation, and cellular function modulation. This Perspective explores the emerging role of DNs in modulating cellular behavior through organelle-targeted interventions. We highlight current advances in nuclear, mitochondrial, and lysosomal targeting, showcasing applications ranging from gene delivery to cancer therapeutics. For instance, DNs have enabled precision mitochondrial disruption in cancer cells, lysosomal pH modulation to enhance gene silencing, and nuclear delivery of gene-editing templates. While DNs hold immense promise for advancing nanomedicine, outstanding challenges include optimizing biological interactions and addressing safety concerns. This Perspective highlights the current potential of DNs for rational control of targeted organelles, which could lead to novel therapeutic strategies and advancement of precision nanomedicines in the future.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

DNA nanostructures (DNs) have gained popularity in various biomedical applications due to their unique properties, including structural programmability, ease of synthesis and functionalization, and low cytotoxicity. Effective utilization of DNs in biomedical applications requires a fundamental understanding of their interactions with living cells and the mechanics of cellular uptake. Current knowledge primarily focuses on how the physicochemical properties of DNs, such as mass, shape, size, and surface functionalization, affect uptake efficacy. However, the role of cellular mechanics and morphology in DN uptake remains largely unexplored. In this work, we show that cells subjected to geometric constraints remodel their actin cytoskeleton, resulting in differential mechanical force generation that facilitates DN uptake. The length, number, and orientation of F-actin fibers are influenced by these constraints, leading to distinct mechanophenotypes. Overall, DN uptake is governed by F-actin forces arising from filament reorganisation under geometric constraints. These results underscore the importance of actin dynamics in the cellular uptake of DNs and suggest that leveraging geometric constraints to induce specific cell morphology adaptations could enhance the uptake of therapeutically designed DNs.

• MeSH
• aktiny metabolismus   chemie   MeSH
• cytoskelet * metabolismus   chemie   MeSH
• DNA * chemie   metabolismus   MeSH
• lidé MeSH
• mikrofilamenta * metabolismus   chemie   MeSH
• nanostruktury * chemie   MeSH
• povrchové vlastnosti MeSH
• velikost částic MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aktiny MeSH
• DNA * MeSH

DNA nanotechnology is a rapidly growing field that provides exciting tools for biomedical applications. Targeting lysosomal functions with nanomaterials, such as DNA nanostructures (DNs), represents a rational and systematic way to control cell functionality. Here we present a versatile DNA nanostructure-based platform that can modulate a number of cellular functions depending on the concentration and surface decoration of the nanostructure. Utilizing different peptides for surface functionalization of DNs, we were able to rationally modulate lysosomal activity, which in turn translated into the control of cellular function, ranging from changes in cell morphology to modulation of immune signaling and cell death. Low concentrations of decalysine peptide-coated DNs induced lysosomal acidification, altering the metabolic activity of susceptible cells. In contrast, DNs coated with an aurein-bearing peptide promoted lysosomal alkalization, triggering STING activation. High concentrations of decalysine peptide-coated DNs caused lysosomal swelling, loss of cell-cell contacts, and morphological changes without inducing cell death. Conversely, high concentrations of aurein-coated DNs led to lysosomal rupture and mitochondrial damage, resulting in significant cytotoxicity. Our study holds promise for the rational design of a new generation of versatile DNA-based nanoplatforms that can be used in various biomedical applications, like the development of combinatorial anti-cancer platforms, efficient systems for endolysosomal escape, and nanoplatforms modulating lysosomal pH.

• Klíčová slova
• DNA nanotechnology, Interferon, Lysosomal rupture, Nanotechnology, bio/nano interactions, lysosome interference,
• Publikační typ
• časopisecké články MeSH

In recent years, it has been recognized that mechanical forces play an important regulative role in living organisms and possess a direct impact on crucial cell functions, ranging from cell growth to maintenance of tissue homeostasis. Advancements in mechanobiology have revealed the profound impact of mechanical signals on diverse cellular responses that are cell type specific. Notably, numerous studies have elucidated the pivotal role of different mechanical cues as regulatory factors influencing various cellular processes, including cell spreading, locomotion, differentiation, and proliferation. Given these insights, it is unsurprising that the responses of cells regulated by physical forces are intricately linked to the modulation of nanoparticle uptake kinetics and processing. This complex interplay underscores the significance of understanding the mechanical microenvironment in shaping cellular behaviors and, consequently, influencing how cells interact with and process nanoparticles. Nevertheless, our knowledge on how localized physical forces affect the internalization and processing of nanoparticles by cells remains rather limited. A significant gap exists in the literature concerning a systematic analysis of how mechanical cues might bias the interactions between nanoparticles and cells. Hence, our aim in this review is to provide a comprehensive and critical analysis of the existing knowledge regarding the influence of mechanical cues on the complicated dynamics of cell-nanoparticle interactions. By addressing this gap, we would like to contribute to a detailed understanding of the role that mechanical forces play in shaping the complex interplay between cells and nanoparticles.

• Klíčová slova
• Extracellular matrix, Mechanical cues, Mechanotransduction, Nanomedicine; Nanoparticles,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Iron oxide nanoparticles (IONPs) are being actively researched in various biomedical applications, particularly as magnetic resonance imaging (MRI) contrast agents for diagnosing various liver pathologies like nonalcoholic fatty liver diseases, nonalcoholic steatohepatitis, and cirrhosis. Emerging evidence suggests that IONPs may exacerbate hepatic steatosis and liver injury in susceptible livers such as those with nonalcoholic fatty liver disease. However, our understanding of how IONPs may affect steatotic cells at the sub-cellular level is still fragmented. Generally, there is a lack of studies identifying the molecular mechanisms of potential toxic and/or adverse effects of IONPs on "non-heathy" in vitro models. In this study, we demonstrate that IONPs, at a dose that does not cause general toxicity in hepatic cells (Alexander and HepG2), induce significant toxicity in steatotic cells (cells loaded with non-toxic doses of palmitic acid). Mechanistically, co-treatment with PA and IONPs resulted in endoplasmic reticulum (ER) stress, accompanied by the release of cathepsin B from lysosomes to the cytosol. The release of cathepsin B, along with ER stress, led to the activation of apoptotic cell death. Our results suggest that it is necessary to consider the interaction between IONPs and the liver, especially in susceptible livers. This study provides important basic knowledge for the future optimization of IONPs as MRI contrast agents for various biomedical applications.

• Publikační typ
• časopisecké články MeSH

DNA nanotechnology has yielded remarkable advances in composite materials with diverse applications in biomedicine. The specificity and predictability of building 3D structures at the nanometer scale make DNA nanotechnology a promising tool for uses in biosensing, drug delivery, cell modulation, and bioimaging. However, for successful translation of DNA nanostructures to real-world applications, it is crucial to understand how they interact with living cells, and the consequences of such interactions. In this review, we summarize the current state of knowledge on the interactions of DNA nanostructures with cells. We identify key challenges, from a cell biology perspective, that influence progress towards the clinical translation of DNA nanostructures. We close by providing an outlook on what questions must be addressed to accelerate the clinical translation of DNA nanostructures. STATEMENT OF SIGNIFICANCE: Self-assembled DNA nanostructures (DNs) offers unique opportunities to overcome persistent challenges in the nanobiotechnology field. However, the interactions between engineered DNs and living cells are still not well defined. Critical systematization of current cellular models and biological responses triggered by DNs is a crucial foundation for the successful clinical translation of DNA nanostructures. Moreover, such an analysis will identify the pitfalls and challenges that are present in the field, and provide a basis for overcoming those challenges.

• Klíčová slova
• Bionano interactions, Cellular uptake, Cytotoxicity, DNA nanotechnology, Nanotechnology, Protein corona,
• MeSH
• DNA chemie   MeSH
• lékové transportní systémy metody   MeSH
• nanostruktury * chemie   MeSH
• nanotechnologie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• DNA MeSH

DNA nanostructures (DNs) can be designed in a controlled and programmable manner, and these structures are increasingly used in a variety of biomedical applications, such as the delivery of therapeutic agents. When exposed to biological liquids, most nanomaterials become covered by a protein corona, which in turn modulates their cellular uptake and the biological response they elicit. However, the interplay between living cells and designed DNs are still not well established. Namely, there are very limited studies that assess protein corona impact on DN biological activity. Here, we analyzed the uptake of functionalized DNs in three distinct hepatic cell lines. Our analysis indicates that cellular uptake is linearly dependent on the cell size. Further, we show that the protein corona determines the endolysosomal vesicle escape efficiency of DNs coated with an endosome escape peptide. Our study offers an important basis for future optimization of DNs as delivery systems for various biomedical applications.

• Klíčová slova
• DNA nanotechnology, bionano interactions, cellular uptake, endolysosomal escape, nanotechnology, protein corona,
• MeSH
• adsorpce MeSH
• DNA chemie   metabolismus   MeSH
• endozomy metabolismus   MeSH
• kationické antimikrobiální peptidy chemie   metabolismus   MeSH
• konformace nukleové kyseliny MeSH
• lidé MeSH
• lyzozomy metabolismus   MeSH
• nádorové buněčné linie MeSH
• nanostruktury chemie   MeSH
• proteinová korona chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aurein 1.2 peptide MeSH Prohlížeč
• DNA MeSH
• kationické antimikrobiální peptidy MeSH
• proteinová korona MeSH

Dextran-coated magnetic nanoparticles are promising biocompatible agents in various biomedical applications, including hyperthermia and magnetic resonance imaging (MRI). However, the influence of dextran molecular weight on the physical properties of dextran-coated magnetic nanoparticles has not been described sufficiently. We synthesise magnetite nanoparticles with a dextran coating using a co-precipitation method and study their physical properties as a function of dextran molecular weight. Several different methods are used to determine the size distribution of the particles, including microscopy, dynamic light scattering, differential centrifugal sedimentation and magnetic measurements. The size of the dextran-coated particles increases with increasing dextran molecular weight. We find that the molecular weight of dextran has a significant effect on the particle size, efficiency, magnetic properties and specific absorption rate. Magnetic hyperthermia measurements show that heating is faster for dextran-coated particles with higher molecular weight. The different molecular weights of the coating also significantly affected its MRI relaxation properties, especially the transversal relaxivity r2. Linear regression analysis reveals a statistically significant dependence of r2 on the differential centrifugal sedimentation diameter. This allows the targeted preparation of dextran-coated magnetic nanoparticles with the desired MRI properties. These results will aid the development of functionalised magnetic nanoparticles for hyperthermia and MRI applications.

• Klíčová slova
• MRI, dextran, diameter, magnetic fluid, magnetic hyperthermia, magnetic nanoparticles, physical properties, relaxivity,
• Publikační typ
• časopisecké články MeSH