Introduction: IL-17 plays an important role in autoimmunity, promoting autoimmunity, inflammation and invasion in multiple sclerosis, rheumatoid arthritis and type I diabetes. The role of IL-17 in cancer is unclear, however, as there are few studies examining IL-17 protein expression in cancer. We therefore examined IL-17 protein expression in human breast cancer and modelled its potential biological significance in vitro. Methods: Immunohistochemistry was used to determine IL-17 expression in breast cancers. Matrigel invasion assays were employed to examine the effect of IL-17 on cancer cell invasion by a panel of breast cancer cell lines. The role of matrix metalloproteinases (MMPs) was investigated with selective antagonists and immunoassays for MMP-2, MMP-3, MMP-9 and tissue inhibitor of MMP. Results: IL-17-expressing cells with macrophage morphology were identified in the peritumoural area of a proportion of patients (8/19 patients). Macrophages were confirmed by CD68 staining on serial sections. With the exception of occasional lymphocytes, one patient with rare multinucleate giant cells and one patient with occasional expression of IL-17 in tumour cells, no other IL-17-positive cells were detected. Addition of IL-17 to cell lines in vitro stimulated marked invasion of Matrigel. In contrast, IL-17 did not promote the invasion of MCF7 or T47D cell lines. Invasion was initially thought to be dependent on MMPs, as evidenced by the broad-spectrum MMP inhibitor GM6001 and selective antagonists of MMP-2/MMP-9 and MMP-3. Measurement of MMP-2, MMP-3 and MMP-9, and tissue inhibitor of MMP 1 secretion, failed to reveal any changes in expression following IL-17 exposure. In contrast, TNF promoted secretion of MMPs but IL-17 did not augment TNF, indicating that IL-17 acts via an independent mechanism. Conclusions: The present study is the first to describe in situ expression of IL-17 protein in human breast tumours and to propose a direct association between IL-17 and breast cancer invasion. The precise effectors of IL-17-dependent invasion remain to be characterised but could include a range of proteases such as a disintegrin and metalloproteinase protein or astacins. Nevertheless, this work identifies a novel potential mechanism for breast cancer invasion and tumour progression, the prognostic implication of which is currently under investigation.

Cancer is one of the leading causes of death in the world. Therefore, the development of new advanced and targeted strategies in cancer research for early diagnosis and treatment has become essential to improve diagnosis outcomes and reduce therapy side effects. Graphene and, more recently, MXene, are the main representatives of the family of two-dimensional (2D) materials, and are widely studied as multimodal nanoplatforms for cancer diagnostics and treatment, in particular leveraging their potentialities as photodynamic therapeutic agents. Indeed, due to their irreplaceable physicochemical properties, they are virtuous allies for photodynamic therapy (PDT) in combination with bioimaging, photothermal therapy, as well as drug and gene delivery. In this review, the rapidly progressing literature related to the use of these promising 2D materials for cancer theranostics is described in details, highlighting all their possible future advances in PDT.

This study describes the previously unreported intrinsic capacity of poly-L-lysine (PLL) sixth generation (G(6)) dendrimer molecules to exhibit systemic antiangiogenic activity that could lead to solid tumor growth arrest. The PLL-dendrimer-inhibited tubule formation of SVEC4-10 murine endothelial cells and neovascularization in the chick embryo chick chorioallantoic membrane (CAM) assay. Intravenous administration of the PLL-dendrimer molecules into C57BL/6 mice inhibited vascularisation in Matrigel plugs implanted subcutaneously. Antiangiogenic activity was further evidenced using intravital microscopy of tumors grown within dorsal skinfold window chambers. Reduced vascularization of P22 rat sarcoma implanted in the dorsal window chamber of SCID mice was observed following tail vein administration (i.v.) of the PLL dendrimers. Also, the in vivo toxicological profile of the PLL-dendrimer molecules was shown to be safe at the dose regime studied. The antiangiogenic activity of the PLL dendrimer was further shown to be associated with significant suppression of B16F10 solid tumor volume and delayed tumor growth. Enhanced apoptosis/necrosis within tumors of PLL-dendrimer-treated animals only and reduction in the number of CD31 positive cells were observed in comparison to protamine treatment. This study suggests that PLL-dendrimer molecules can exhibit a systemic antiangiogenic activity that may be used for therapy of solid tumors, and in combination with their capacity to carry other therapeutic or diagnostic agents may potentially offer capabilities for the design of theranostic systems.

One of the major obstacles to the clinical development of gene silencing by small interfering RNA (siRNA) is its effective cytoplasmic delivery. Carbon nano‐tubes have been proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We recently demonstrated in a proof‐of‐principle study that amino‐functionalized multiwalled carbon nanotubes ( f‐ MWNT) can effectively deliver in vivo an siRNA sequence, triggering cell apoptosis that results in human lung xenograft eradication and prolonged survival. In the present study, we demonstrate how a newly synthesized series of polycationic dendron‐MWNT constructs with a precisely tailored number of amino functions (dendron generations) can complex and effectively deliver double‐stranded siRNA to achieve gene silencing in vitro . A systematic comparison between the f‐ MWNT series in terms of cellular uptake, cytotoxicity, and siRNA complexation is offered. Significant improvement in siRNA delivery with the dendron‐MWNT conjugates is shown, and gene silencing was obtained in 2 human cell lines using 2 different siRNA sequences. The study reveals that through f‐ MWNT structure‐biological function analysis novel nanotube‐based siRNA transfer vectors can be designed with minimal cytotoxicity and effective delivery and gene‐silencing capabilities.—Al‐Jamal, K. T., Toma, F. M., Yilmazer, A., Ali‐Boucetta, H., Nunes, A., Herrero, M.‐A., Tian, B., Eddaoudi, A., Al‐Jamal, W. T., Bianco, A., Prato, M., Kostarelos, K. Enhanced cellular internalization and gene silencing with a series of cationic dendron‐multiwalled carbon nanotube:siRNA complexes. FASEB J . 24, 4354–4365 (2010). www.fasebj.org