Photoresponsive nanosystems for therapeutic applications

Oncological and bacterial diseases are certainly the most troubling illnesses of the twenty-first century, and the data in this regard are staggering. Indeed, anticancer chemotherapy is affected by low specificity/selectivity and undesired side effects, and drug resistance phenomena are responsible for the failure of many conventional treatments. Multidrug-resistant-bacteria (MDRB) infection is become another burden to modern healthcare. For such a reason, there is an increasing demand for the development of new strategies for anticancer and antibacterial treatments without antibiotics to save millions of lives every year.1 In this frame, the light-controlled generation of cytotoxic species, such as singlet oxygen (1O2) and nitric oxide (NO), by using appropriate photochemical precursors represents a fascinating and unconventional approach for the treatment of cancerous and microbial diseases in non-invasive manner. However, many precursors have a hydrophobic nature, which favors their aggregation in aqueous medium strongly precluding their photochemical behavior.2 The entrapment of drugs and pro-drugs in nanocarriers permits to overcome all these drawbacks and ensures protection from degradation, site-specific delivery, enhanced bioavailability, increased local concentration. Here in are reported studies of two different types of nanocarriers carrying different photoactivable guests. The first part of this dissertation focuses on the achievement of novel photoresponsive calix[4]arene-based nanoconstructs which vehicle, by not covalent or covalent approach, different kinds of chromophores. The second part concerns the design, synthesis, antitumoral and antibacterial activity of polymersomes containing a nitric oxide photoprecursor by covalent and non-covalent approach

A phototherapeutic fluorescent β-cyclodextrin branched polymer delivering nitric oxide

We report herein on a novel water-soluble β-cyclodextrinbranched polymer covalently integrating a fluorescein moiety and a nitric oxide (NO) photodonor within its macromolecular skeleton. Photoexcitation with visible light induces the parallel activation of the two chromophores, which results in the green fluorescence emission suitable for imaging accompanied by NO release for therapy. In fact, this polymer internalizes in squamous carcinoma cancer cells in vitro, visualized by fluorescence microscopy, and induces cell mortality as result of the NO photo-decaging. The non-covalent drug delivery capability of this new material is also demonstrated using a hydrophobic photosensitizer for photodynamic therapy as a probe

Where Brain, Body and World Collide

The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| < 0.8) in the transverse momentum range 1 < pt < 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs

Polymer and water dynamics in Poly(vinyl alcohol)/Poly(methacrylate) networks. A molecular dynamics simulation and incoherent neutron scattering investigation

Chemically cross-linked polymer networks of poly(vinyl alcohol)/poly(methacrylate) form monolitic hydrogels and microgels suitable for biomedical applications, such as in situ tissue replacement and drug delivery. In this work, molecular dynamics (MD) simulation and incoherent neutron scattering methods are used to study the local polymer dynamics and the polymer induced modification of water properties in poly(vinyl alcohol)/poly(methacrylate) hydrogels. This information is particularly relevant when the diffusion of metabolites and drugs is a requirement for the polymer microgel functionality. MD simulations of an atomic detailed model of the junction domain at the experimental hydration degree were carried out at 283, 293 and 313 K. The polymer-water interaction, the polymer connectivity and the water dynamics were investigated as a function of temperature. Simulation results are compared with findings of elastic and quasi-elastic incoherent neutron scattering measurements, experimental approaches which sample the same space-time window of MD simulations. This combined analysis shows a supercooled water component and an increase of hydrophilicity and mobility with temperature of these amphiphilic polymer networks

Metabolic control and complications in Italian people with diabetes treated with continuous subcutaneous insulin infusion

The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII)