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• Intratumoral administration enables local drug delivery and low systemic toxicity. • Injectable hydrogels are minimally invasive and promote drug retention in tumors. • Hydrogels may undergo phase transition or structural change in response to stimuli. • Stimuli are exogenous (light) or endogenous triggers in the tumor microenvironment. The ability of some hydrogels to exhibit a phase transition or change their structure in response to stimuli has been extensively explored for drug depot formation and controlled drug release. Taking advantage of the unique features of the tumor microenvironment (TME) or externally applied triggers, several injectable stimuli-responsive hydrogels have been described as promising candidates for intratumoral drug delivery. In this review, we provide a brief overview of the TME and highlight the advantages of intratumoral administration, followed by a summary of the reported strategies to endow hydrogels with responsiveness to physical (temperature and light), chemical (pH and redox potential), or biological (enzyme) stimuli. [ABSTRACT FROM AUTHOR]

Alternative pre-mRNA splicing (AS) affects gene expression as it generates proteome diversity. Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selectively degrades mRNAs carrying premature translation-termination codons (PTCs), preventing the production of truncated proteins that could result in disease. Several studies have also implicated NMD in the regulation of steady-state levels of physiological mRNAs. In addition, it is known that several regulated AS events do not lead to generation of protein products, as they lead to transcripts that carry PTCs and thus, they are committed to NMD. Indeed, an estimated one-third of naturally occurring, alternatively spliced mRNAs is targeted for NMD, being AS coupled to NMD (AS-NMD) an efficient strategy to regulate gene expression. In this review, we will focus on how AS mechanism operates and how can be coupled to NMD to fine-tune gene expression levels. Furthermore, we will demonstrate the physiological significance of the interplay among AS and NMD in human disease, such as cancer and neurological disorders. The understanding of how AS-NMD orchestrates expression of vital genes is of utmost importance for the advance in diagnosis, prognosis and treatment of many human disorders. [ABSTRACT FROM AUTHOR]

Topical drug delivery in the oral mucosa has its set of challenges due to the unique anatomical and physiological features of the oral cavity. As such, the outcomes of local pharmacological treatments in oral disorders can fail due to unsuccessfully drug delivery. Oral mucositis, a severe inflammatory and ulcerative side effect of oncological treatments, is one of such diseases. Although the damaged tissue is within reach, no approved topical drug treatment is available. Several strategies based on its physiopathology have been implemented and clinically used. Even so, results tend to lack or be insufficient to improve patient's quality of life. The use of corticosteroids has been employed in such strategies due to their strong anti-inflammatory action. Typically, these are administrated in simple liquid formulations, where the drug is dispersed or solubilized, lacking the ability to maintain local concentration. In this work, we propose the development of a biocompatible delivery system with boosted abilities of retention and control release of budesonide, a corticosteroid with an elevated ratio of topical anti-inflammatory to systemic action. Through spray-drying, polymeric particles of Chitosan and Eudragit® E PO were produced and characterized for the vectorization of this drug. [ABSTRACT FROM AUTHOR]

A new family of copper(I) complexes of general formula [Cu(dppe)(NN)] + have been synthesized and fully characterized, with dppe = 1.2-bis(diphenylphosphino)ethane and NN representing several bidentate heteroaromatic ligands: 2,2′-bipy = 2.2′-bipyridine (1), Me 2 bpy = 4.4′-dimethyl-2,2′-bipyridine (2), dpytz = 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (3), dpp = 2.3-bis(2-pyridyl)pyrazine (4), and the metallaligand [Ru(η 5 -C 5 H 5 )(PPh 3 )(dpp)] + (5), yielding the bimetallic copper(I)-ruthenium(II) complex [Cu(dppe)(μ-dpp)Ru(η 5 -C 5 H 5 )(PPh 3 )] 2 + (6). The single crystal structures of complexes (2) and (4) were determined by X-ray diffraction studies. All the complexes exhibit high cytotoxicity against the human cancer cells A2780 and MCF7 with IC 50 values far lower than those found for the antitumor drug cisplatin in the same cell lines and even surpassing cisplatin resistance in the A2780cisR cells. They display IC 50 values on the human embryonic kidney HEK293 non-tumoral cells of the same order of magnitude as those found for the tumoral cells. In the ovarian cells the compounds induce rapid production of reactive oxygen species (ROS) probably through mitochondrial pathways. According to the results reported here, these compounds can be considered as prospective antitumoral agents that deserve further evaluation. [ABSTRACT FROM AUTHOR]

Abstract: The rigid [6]ferrocenophane, L1, was synthesised by condensation of 1,1′-ferrocene dicarbaldehyde with trans-1,2-diaminocyclohexane in high dilution at r.t. followed by reduction. When other experimental conditions were employed, the [6,6,6]ferrocenephane (L2) was also obtained. Both compounds were characterised by single crystal X-ray crystallography. The protonation of L1 and its metal complexation were evaluated by the effect on the electron-transfer process of the ferrocene (fc) unit of L1 using cyclic voltammetry (CV) and square wave voltammetry (SWV) in anhydrous CH3CN solution and in 0.1 M n Bu4NPF6 as the supporting electrolyte. The electrochemical process of L1 between −300 and 900mV is complicated by amine oxidation. On the other hand, an anodic shift from the fc/fc+ wave of L1 of 249, 225, 81 and 61mV was observed by formation of Zn2+, Ni2+, Pd2+ and Cu2+ complexes, respectively. Whereas Mg2+ and Ca2+ only have with L1 weak interactions and they promote the acid-base equilibrium of L1. This reveals that L1 is an interesting molecular redox sensor for detection of Zn2+ and Ni2+, although the kinetics of the Zn2+ complex formation is much faster than that of the Ni2+ one. The X-ray crystal structure of [PdL1Cl2] was determined and showed a square–planar environment with Pd(II) and Fe(II) centres separated by 3.781(1)Å. The experimental anodic shifts were elucidated by DFT calculations on the [ML1Cl2] series and they are related to the nature of the HOMO of these complexes and a four-electron, two-orbital interaction. [Copyright &y& Elsevier]