Tumor ablation by thermal energy via the irradiation of plasmonic nanoparticles is a relatively new oncology treatment. Hybrid plasmonic‐superparamagnetic nanoaggregates (50–100 nm in diameter) consisting of SiO2‐coated Fe2O3 and Au (≈30 nm) nanoparticles were fabricated using scalable flame aerosol technology. By finely tuning the Au interparticle distance using the SiO2 film thickness (or content), the plasmonic coupling of Au nanoparticles can be finely controlled bringing their optical absorption to the near‐IR that is most important for human tissue transmittance. The SiO2 shell facilitates also dispersion and prevents the reshaping or coalescence of Au particles during laser irradiation, thereby allowing their use in multiple treatments. These nanoaggregates have magnetic resonance imaging (MRI) capability as shown by measuring their r2 relaxivity while their effectiveness as photothermal agents is demonstrated by killing human breast cancer cells with a short, four minute near‐IR laser irradiation (785 nm) at low flux (4.9 W cm‐2).
Lymphatic vessels play important roles in fluid drainage and in immune responses, as well as in pathological processes including cancer progression and inflammation. While the molecular regulation of the earliest lymphatic vessel differentiation and development has been investigated in much detail, less is known about the control and timing of lymphatic vessel maturation in different organs, which often occurs postnatally. We investigated the time course of lymphatic vessel development on the pleural side of the diaphragmatic muscle in mice, the so-called submesothelial initial diaphragmatic lymphatic plexus. We found that this lymphatic network develops largely after birth and that it can serve as a reliable and easily quantifiable model to study physiological lymphangiogenesis in vivo. Lymphangiogenic growth in this tissue was highly dependent on vascular endothelial growth factor receptor (VEGFR)-3 signaling, whereas VEGFR-1 and -2 signaling was dispensable. During diaphragm development, macrophages appeared first in a linearly arranged pattern, followed by ingrowth of lymphatic vessels along these patterned lines. Surprisingly, ablation of macrophages in colony-stimulating factor-1 receptor (Csf1r)-deficient mice and by treatment with a CSF-1R-blocking antibody did not inhibit the general lymphatic vessel development in the diaphragm but specifically promoted branch formation of lymphatic sprouts. In agreement with these findings, incubation of cultured lymphatic endothelial cells with conditioned medium from P7 diaphragmatic macrophages significantly reduced LEC sprouting. These results indicate that the postnatal diaphragm provides a suitable model for studies of physiological lymphangiogenic growth and maturation, and for the identification of modulators of lymphatic vessel growth.Electronic supplementary materialThe online version of this article (doi:10.1007/s10456-016-9523-8) contains supplementary material, which is available to authorized users.
Encapsulating chemotherapeutics in nanoparticles can reduce the side effects of intravenous administration and improve their antitumor efficacy. Additionally, surface decoration of the nanocarriers with tumor-targeting ligands may enhance their specificity for cancer cells overexpressing the corresponding ligand-binding counterpart. The focus here is on anisamide, a low-molecular-weight benzamide derivative used as a tumor-directing moiety in functionalized nanosystems, based on its alleged interaction with Sigma receptors. The scintigraphic agents that initially inspired the use of anisamide for tumor targeting are described, and the published anisamide-tethered nanocarrier formulations are reviewed, together with a critical overview of the ligand's tumor-targeting properties. Moreover, anisamide's putative but dubious cellular target, the Sigma-1 receptor, is discussed with regard to its subcellular localization and implications in cancer. Data from in vivo studies reveal that the effect of anisamide on the antitumor efficacy of the decorated nanosystems varies considerably among the published reports. Together with the evidence questioning the interaction of anisamide with the Sigma receptors, the variability of anisamide's effect on the tumor deposition and the antitumor efficacy of the decorated drug carriers calls into question the extent of the ligand's tumor-targeting effect. Further research is necessary to elucidate the ligand's utility in tumor targeting.
Drug delivery is considered a mature scientific and technological platform for producing innovative medicines with nanosystems composed of intelligent bio-materials that carry active pharmaceutical ingredients forming advanced drug delivery nanosystems (aDDnSs). Shikonin and its enantiomer alkannin are natural products that have been extensively studied in vitro and in vivo for, among others, their antitumor activity, and various efforts have been made to prepare shikonin-loaded drug delivery systems. This study is focused on chimeric aDDnSs and specifically on liposomal formulations combining three lipids (egg-phosphatidylcholine; dipalmitoyl phosphatidylcholine; and distearoyl phosphatidylcholine) and a hyperbranched polymer (PFH-64-OH). Furthermore, PEGylated liposomal formulations of all samples were also prepared. Calorimetric techniques and electron paramagnetic resonance were used to explore and evaluate the interactions and stability of the liposomal formulations, showing that the presence of hyperbranched polymers promote the overall stability of the chimeric aDDnSs based on the drug release profile enhancement. Furthermore, results showed that polyethylene glycol enhances drug stabilization inside the liposomes, forming a stable and promising carrier for shikonin with improved characteristics.
CD26, also known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin. However, only scarce data are available regarding the distribution and function of this protein in the human skin. Therefore, the aim of this study was to investigate the impact of CD26 deficiency in human primary fibroblasts on the regeneration of human tissue-engineered skin substitutes in vivo. Dermo-epidermal skin analogs, based on collagen type I hydrogels, were populated either with human CD26+ or CD26knockout fibroblasts and seeded with human epidermal keratinocytes. These skin substitutes were transplanted onto the back of immune-incompetent rodents. Three weeks post-transplantation, the grafts were excised and analyzed with respect to specific epidermal and dermal maturation markers. For the first time, we show here that the expression of CD26 protein in human dermis is age-dependent. Furthermore, we prove that CD26+ fibroblasts are more active in the production of extracellular matrix (ECM) both in vitro and in vivo and are necessary to achieve rapid epidermal and dermal homeostasis after transplantation.
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