Screening the Cytotoxicity of Single-Walled Carbon Nanotubes Using Novel 3D Tissue-Mimetic Models

Single-walled carbon nanotubes (SWNTs) are promising candidates for a wide range of biomedical applications due to their fascinating properties. However, safety concerns are raised on their potential human toxicity and on the techniques that need to be used to assess such toxicity. Here, we integrate for the first time 3D tissue-mimetic models in the cytotoxicity assessment of purified (p-) and oxidized (o-) SWNTs. An established ultrasound standing wave trap was used to generate the 3D cell aggregates, and results were compared with traditional 2D cell culture models. Protein-based (bovine serum albumin) and surfactant-based (Pluronic F68) nanotube dispersions were tested and compared to a reference suspension in dimethyl sulfoxide. Our results indicated that p- and o-SWNTs were not toxic in the 3D cellular model following a 24 h exposure. In contrast, 2D cell cultures were significantly affected by exposure to p- and o-SWNTs after 24 h, as assessed by high-content screening and analysis (HCSA). Finally, cytokine (IL-6 and TNF-α) secretion levels were elevated in the 2D but remained essentially unchanged in the 3D cell models. Our results strongly indicate that 3D cell aggregates can be used as alternative <i>in vitro</i> models providing guidance on nanomaterial toxicity in a tissue-mimetic manner, thus offering future cost-effective solutions for toxicity screening assays under the experimental conditions more closely related to the physiological scenario in 3D tissue microenvironments

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Figure raw data and statitistical analysi

Tunable Design of Gold(III)–Doxorubicin Complex–PEGylated Nanocarrier. The Golden Doxorubicin for Oncological Applications

To date, the translation of Au (III) complexes into chemotherapeutic agents has been hindered by their low stability under physiological conditions, a crucial parameter in drug development. In this study, we report an innovative four-step synthesis of a stable Au (III)–doxorubicin (DOX) complex, acting as a key constitutive component of doxorubicin-loaded PEG-coated nanoparticles (DOX IN–PEG–AuNPs). For therapeutic purposes, such AuNPs were then functionalized with the anti-K_v11.1 polyclonal antibody (pAb), which specifically recognizes the hERG1 channel that is overexpressed on the membrane of human pancreatic cancer cells. The nature of the interactions between DOX and Au (III) ions was probed by various analytical techniques (Raman spectroscopy, UV–vis, and ¹H NMR), which enabled studying the Au (III)–DOX interactions during AuNPs formation. The theoretical characterization of the vibrational bands and the electronic transitions of the Au (III)–DOX complex calculated through computational studies showed significant qualitative agreement with the experimental observations on AuNPs samples. Stability in physiological conditions and efficient drug loading (up to to 85 w/w %) were achieved, while drug release was strongly dependent on the structure of DOX IN–PEG–AuNPs and on the pH. Furthermore, the interactions among DOX, PEG, and Au (III) ions in DOX IN–PEG–AuNPs differed significantly from those found in polymer-modified AuNPs loaded with DOX by covalent linkage, referred to as DOX ON–PEG–AuNPs. <i>In vitro</i> experiments indeed demonstrated that such differences strongly influenced the therapeutic potential of AuNPs in pancreatic cancer treatment, with a significant increase of the DOX therapeutic index when complexed to Au (III) ions. Collectively, our study demonstrated that Au (III)–DOX complexes as building blocks of PEGylated AuNPs constitutes a promising approach to transform promising Au (III) complexes into real chemotherapeutic drugs for the treatment of pancreatic cancer

Supplementary Information from Silver nanoparticles as a medical device in healthcare settings: a five-step approach for candidate screening of coating agents

Additional information on: Ag+ collection and quantification; HF5 separation and characterisation; Cytokine secretion

Highly Sensitive Single Domain Antibody–Quantum Dot Conjugates for Detection of HER2 Biomarker in Lung and Breast Cancer Cells

Despite the widespread availability of immunohistochemical and other methodologies for screening and early detection of lung and breast cancer biomarkers, diagnosis of the early stage of cancers can be difficult and prone to error. The identification and validation of early biomarkers specific to lung and breast cancers, which would permit the development of more sensitive methods for detection of early disease onset, is urgently needed. In this paper, ultra-small and bright nanoprobes based on quantum dots (QDs) conjugated to single domain anti-HER2 (human epidermal growth factor receptor 2) antibodies (sdAbs) were applied for immunolabeling of breast and lung cancer cell lines, and their performance was compared to that of anti-HER2 monoclonal antibodies conjugated to conventional organic dyes Alexa Fluor 488 and Alexa Fluor 568. The sdAbs–QD conjugates achieved superior staining in a panel of lung cancer cell lines with differential HER2 expression. This shows their outstanding potential for the development of more sensitive assays for early detection of cancer biomarkers

MOESM1 of The protective association of endogenous immunoglobulins against sepsis mortality is restricted to patients with moderate organ failure

Additional file 1. Mean survival time (days) in the SOFA <8 group based on immunoglobulin thresholds. Differences between groups were assessed using the log-rank test. Δ (days) represents [(mean survival time in patients with levels of immunoglobulin above the threshold) – (mean survival time in patients with levels of immunoglobulin below the threshold)]. Time was censored at 28 days following ICU admissio