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- Bölükbas, D. A., et al.
(author)
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Fine-tuning lung cancer nanotherapy using closed cardiopulmonary circulation
- 2019
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In: Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium : 42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence - 42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence. - 9781510883901 ; 40
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Conference paper (peer-reviewed)abstract
- Statement of Purpose: Lung cancer is the leading cause of cancer-related deaths and efficient therapies remain elusive. One emerging approach is to use nanoparticles (NPs) that are designed to specifically target malignant cells (1). Such targeting increases on-site drug doses and reduces systemic side effects. A common target in lung tumors is epidermal growth factor receptor (EGFR). Here, we explored the targeting efficacy of EGFR-targeted mesoporous silica nanoparticles (MSN GE11 ) for lung cancer treatment. Though specifically taken up by cancer cells in vitro, when administered intravenously or intratracheally in lung cancer mouse models, the NPs could not reach the depths of solid tumors and often strayed away from their target. This raises concerns whether NPs are suitable for therapeutically targeting lung tumors and challenges translational value of current approaches. To circumvent physiological barriers of solid lung tumors and consequent systemic clearance of NPs, we extended our analysis to a treatment strategy where the NPs are administered intravenously in a closed cardiopulmonary (CP) circulation loop. This approach not only makes the therapy more local, but also eliminates confounding factors for NP delivery such as liver/spleen deposition of NPs in vivo.
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- de Ávila, Renato Ivan, et al.
(author)
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Evaluation of in vitro testing strategies for hazard assessment of the skin sensitization potential of “real-life” mixtures : The case of henna-based hair-colouring products containing p-phenylenediamine
- 2019
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In: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 81:3, s. 194-209
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Journal article (peer-reviewed)abstract
- Background: Allergic contact dermatitis caused by henna-based hair-colouring products has been associated with adulteration of henna with p-phenylenediamine (PPD). Objectives: To develop a testing approach based on in vitro techniques that address key events within the skin sensitization adverse outcome pathway in order to evaluate the allergenic potential of hair-colouring products. Methods: The following in vitro assays were used to test the sensitizing capacity of hair dye ingredients: the micro-direct peptide reactivity assay (mDPRA); the HaCaT keratinocyte-associated interleukin (IL)-18 assay; the U937 cell line activation test (U-SENS)/IL-8 levels; the blood monocyte-derived dendritic cell test; and genomic allergen rapid detection (GARD skin). Those techniques with better human concordance were selected to evaluate the allergenic potential of 10 hair-colouring products. Results: In contrast to the information on the label, chromatographic analyses identified PPD in all products. The main henna biomarker, lawsone, was not detected in one of the 10 products. Among the techniques evaluated by testing hair dye ingredients, the mDPRA, the IL-18 assay, GARD skin and the U-SENS correlated better with human classification (concordances of 91.7%-100%) and were superior to the animal testing (concordance of 78.5%). Thus, these assays were used to evaluate hair-colouring products, which were classified as skin sensitizers by the use of different two-of-three approaches. Conclusions: Our findings highlight the toxicological consequences of, and risks associated with, the undisclosed use of PPD in henna-based “natural” “real-life” products.
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