Ln(III) Complexes Embedded in Biocompatible PLGA Nanoparticles as Potential Vis-to-NIR Optical Probes

In this contribution, we present the spectroscopic study of two NIR emitting hydrophobic heteroleptic (R,R)-YbL1(tta) and (R,R)-NdL1(tta) complexes (with tta = 2-thenoyltrifluoroacetonate and L1 = N,N0 -bis(2-(8-hydroxyquinolinate)methylidene)-1,2-(R,R or S,S)-cyclohexanediamine), both in methanol solution and embedded in water dispersible and biocompatible poly lactic-co-glycolic acid (PLGA) nanoparticles. Thanks to their absorption properties in a wide range of wavelengths extending from the UV up to the blue and green visible regions, the emission of these complexes can be effectively sensitized using visible radiation, which is much less harmful to tissues and skin than the UV one. The encapsulation of the two Ln(III)-based complexes in PLGA allows us to preserve their nature, making them stable in water and to test their cytotoxicity on two different cell lines, with the aim of using them in the future as potential bioimaging optical probes

Near Infared Circularly Polarized Luminescence from water stable organic nanoparticles containing a chiral Yb(III) complex

We report the first example of very efficient NIR Circularly Polarized Luminescence (CPL) (around 970 nm) in water, obtained thanks to the combined use of a chiral Yb complex and of poly lactic-co-glycolic acid (PLGA) nanoparticles. [Yb L (tta) 2 ]CH 3 COO ( L = N, N'-bis(2-pyridylmethylidene)-1,2-( R,R + S,S ) cyclohexanediamine and tta = 2-thenoyltrifluoroacetonate) shows good CPL in organic solvents, because the tta ligands efficiently sensitize Yb NIR luminescence and the readily prepared chiral ligand L endows the complex with the necessary dissymmetry. PLGA nanoparticles incorporate the complex and protect the metal ion from the intrusion of solvent molecules, while ensuring biocompatibility, water solubility and stability to the complex. Hydrophilic NIR-CPL optical probes can find applications in the field of NIR-CPL bio-assays

Circularly Polarized Luminescence from New Heteroleptic Eu(III) and Tb(III) Complexes

The complexes [Eu-(bpcd)-(tta)],[Eu-(bpcd)-(Coum)], and [Tb-(bpcd)-(Coum)][tta = 2-thenoyltrifluoroacetyl-acetonate, Coum = 3-acetyl-4-hydroxy-coumarin,and bpcd = N,N '-bis-(2-pyridylmethyl)-trans-1,2-diaminocyclohexane-N,N '-diacetate] have been synthesized and characterizedfrom photophysical and thermodynamic points of view. The optical andchiroptical properties of these complexes, such as the total luminescence,decay curves of the Ln-(III) luminescence, electronic circular dichroism,and circularly polarized luminescence, have been investigated. Interestingly,the number of coordinated solvent (methanol) molecules is sensitiveto the nature of the metal ion. This number, estimated by spectroscopy,is >1 for Eu-(III)-based complexes and <1 for Tb-(III)-based complexes.A possible explanation for this behavior is provided via the studyof the minimum energy structure obtained by density functional theory(DFT) calculations on the model complexes of the diamagnetic Y-(III)and La-(III) counterparts [Y-(bpcd)-(tta)], [Y-(bpcd)-(Coum)], and [La-(bpcd)-(Coum)].By time-dependent DFT calculations, estimation of donor-acceptor(D-A) distances and of the energy position of the S-1 and T-1 ligand excited states involved in the antenna effect was possible. These data are useful for rationalizingthe different sensitization efficiencies (eta(sens))of the antennae toward Eu-(III) and Tb-(III). The ttaligand is an optimal antenna for sensitizing Eu-(III)luminescence, while the Coum ligand sensitizes better Tb-(III) luminescence{phi(ovl) = 55%; eta(sens) >= 55%for the [Tb-(bpcd)-(Coum)] complex}. Finally, for the [Eu-(bpcd)-(tta)]complex, a sizable value of g (lum) (0.26)and a good quantum yield (26%) were measured.Chiral, DACH-based Eu-(III) and Tb-(III) heteroleptic complexesexhibit good metal-centered circularly polarized luminescence activityupon excitation of the antenna ligands. The tta andCoum ligands are optimal antennae for Eu-(III) andTb-(III) luminescence, respectively. The Tb-(III)-based complex showsa very good overall quantum yield of similar to 55%

Association between sex hormones and anti-S/RBD antibody responses to COVID-19 vaccines in healthcare workers

ABSTRACTHealthcare workers (HCWs) are the target population for vaccination against coronavirus disease (COVID-19) as they are at a high risk of exposure and transmission of pathogens to patients. Neutralizing antibodies developed after COVID-19 vaccination decline within few months of vaccination. Several factors, including age and sex, can affect the intensity, efficacy, and duration of immune response to vaccines. However, sex-specific analyses of humoral responses to COVID-19 vaccines are lacking. This study aimed to evaluate sex-based differences in anti-S/RBD (Receptor Binding Domain) responses at three different time points after the second dose of mRNA COVID-19 vaccine in HCWs in relation to age, and to investigate the role of sex hormones as potential markers of response. Anti-S/RBD levels after two doses of the mRNA vaccine were collected from 521 HCWs naïve to COVID-19, working at two Italian Clinical Centers. Multiple regression analysis was applied to evaluate the association between anti-S levels and sex, age, and plasma levels of sex hormones. Significantly higher anti-S/RBD response to the COVID-19 vaccination was found in female HCWs, and a significant and more abrupt decline in response with time was observed in women than that in men. A novel, positive association of testosterone plasma levels and higher anti-S levels in male HCWs was found, suggesting its potential role as sex specific marker in males. In conclusion, understanding the sex-based differences in humoral immune responses to vaccines may potentially improve vaccination strategies and optimize surveillance programs for HCWs

Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study

Introduction: Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types 1–3 SMA. Here, an analysis was performed after all patients had received at least 1 year of treatment with risdiplam. Methods: Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6 months and 60 years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2 years of treatment. Results: A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0 years (1–60 years) and 39.1 kg (9.2–108.9 kg), respectively. About 63% of patients aged 2–60 years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions: The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients