The mild synthetic conditions provided by the sol-gel process and the versatility of the colloidal state allow for the mixing of inorganic and organic components at the nanometre scale in virtually any ratio for the preparation of hybrid materials. Our interest in hybrid xerogels focuses on combining their porosity with other properties to prepare optic-fibre sensors. The specific aim of this paper is to synthesise hybrid xerogels in acid media using methyltriethoxysilane (MTEOS) and tetraethoxysilane (TEOS) as silica precursors and to investigate the effect of the MTEOS molar ratio on the structure and porous texture of xerogels. Gelation time exponentially increased as the MTEOS molar ratio increased. Increasing the MTEOS molar ratio yielded xerogels with lower density and lower particle size. The incorporation of MTEOS resulted in new FTIR bands at 1276 and 791 cm −1 , which was attributed to vibrational modes of methyl group. The band around 1092 cm −1 associated with siloxane bonds shifted to lower wavenumbers and split into two bands. The 29 Si spectra only showed the Q n (n = 2, 3, 4) signal in xerogels with 0% MTEOS and the T n (n = 2, 3) signal in xerogels with 100% MTEOS; hybrid xerogels showed both Q and T signals. From XRD peaks at 2θ around 9°, we inferred that xerogels (>70% MTEOS) consisted of nanocrystalline CH 3 -SiO 3/2 species. Increasing the MTEOS molar ratio produced xerogels with lower pore volumes and lower average pore size. The integration of methyl groups on the surface decreased the surface polarity and, in turn, the characteristic energy.

Triple negative breast cancer (TNBC) is the deadliest form of breast cancer and its successful treatment critically depends on early diagnosis and therapy. The multi-compartment protein p32 is overexpressed and present at cell surfaces in a variety of tumors, including TNBC, specifically in the malignant cells and endothelial cells, and in macrophages localized in hypoxic areas of the tumor. Herein we used polyethylene glycol-polycaprolactone polymersomes that were affinity targeted with the p32-binding tumor penetrating peptide LinTT1 (AKRGARSTA) for imaging of TNBC lesions. A tyrosine residue was added to the peptide to allow for 124I labeling and PET imaging. In a TNBC model in mice, systemic LinTT1-targeted polymersomes accumulated in early tumor lesions more than twice as efficiently as untargeted polymersomes with up to 20% ID/cc at 24 h after administration. The PET-imaging was very sensitive, allowing detection of tumors as small as ∼20 mm3. Confocal imaging of tumor tissue sections revealed a high degree of vascular exit and stromal penetration of LinTT1-targeted polymersomes and co-localization with tumor-associated macrophages. Our studies show that systemic LinTT1-targeted polymersomes can be potentially used for precision-guided tumor imaging and treatment of TNBC.

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Polyelectrolyte multilayers (PEMs) based on biopolyelectrolytes are highly appealing for the surface engineering of biomaterials and the tuning of cell response and phenotypes for biomedical applications. However, cell adhesion is limited on biopolyelectrolyte PEMs. Thermal annealing provides a simple means to increase or decrease cell adhesion on PEMs. The work presented here aims to understand cellular interactions with annealed PEMs based on the adsorption and exchangeability of two model proteins: fibronectin (FN), an adhesion protein, and bovine serum albumin (BSA), a nonadhesion protein. Protein adsorption and exchangeability are studied on annealed poly‐l‐lysine (PLL)/sodium alginate (Alg) and chitosan (Chi)/hyaluronic acid (HA) PEMs using [131I] radiolabeled proteins and gamma counting. Upon annealing cell adhesion is enhanced on PLL/Alg multilayers and decreased on Chi/HA multilayers. For PLL/Alg PEMs, annealing increases adsorption of both FN and BSA and reduces exchangeability. For Chi/HA multilayers, annealing increases BSA adsorption but decreases FN deposition, accompanied by a greater exchangeability. Changes in topographic features of deposited proteins on annealed PLL/Alg hint on changes in the 3D structure of the proteins. Circular dichroism shows that FN retains a large β‐sheet contribution upon adsorption to both annealed and unannealed PLL/Alg PEMs, also suggesting changes in tertiary structure.

It is well settled that the amyloidogenic properties of the plasma protein transporter transthyretin (TTR) can be modulated by compounds that stabilize its native tetrameric conformation. TTR is also present in cerebrospinal fluid where it can bind to Aβ-peptides and prevent Aβ aggregation. We have previously shown that treatment of Alzheimer’s Disease (AD) model mice with iododiflunisal (IDIF), a TTR tetramer stabilizing compound, prevents AD pathologies. This evidence positioned IDIF as a new lead drug for AD. In dissecting the mechanism of action of IDIF, we disclose here different labeling strategies for the preparation of 131I-labeled IDIF and 131I- and 124I-labeled TTR, which have been further used for the preparation of IDIF-TTR complexes labeled either on the compound or the protein. The biodistribution of all labeled species after intravenous administration has been investigated in mice using ex vivo and in vivo techniques. Our results confirm the capacity of TTR to cross the blood brain barrier (BBB) and suggest that the formation of TTR-IDIF complexes enhances BBB permeability of both IDIF and TTR. The increased TTR and IDIF brain concentrations may result in higher Aβ-peptide sequestration capacity with the subsequent inhibition of AD symptoms as we have previously observed in mice.