Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma

\ua9 2024 Author(s).Osteosarcoma (OS) is a rare form of primary bone cancer, impacting approximately 3.4 7 106 individuals worldwide each year, primarily afflicting children. Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades. These platforms seamlessly integrate therapeutic potential of drug compounds with the diagnostic capabilities of imaging probes within a single construct. This innovation has opened avenues for enhanced drug delivery to targeted sites while concurrently enabling real-time monitoring of the vehicle\u27s trajectory. In this study, we developed a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. By utilizing chitosan and chondroitin sulfate as polyelectrolytes, we constructed a multilayered coating to encapsulate DOXO and docetaxel, achieving a coordinated co-delivery of both drugs. The LbL-functionalized nanoparticles exhibited an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs. The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by in vitro release tests. Finally, the impact of the LbL-functionalized nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs was found to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations higher than 10 μg/ml. Transmission electron microscopy analysis confirmed the internalization of the nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death

Capecitabine and Temozolomide (CAPTEM) in advanced neuroendocrine neoplasms (NENs): a systematic review and pooled analysis

Background Retrospective studies and single center experiences suggest a role of capecitabine combined with temozolomide (CAPTEM) in neuroendocrine tumors (NENs). Methods We performed a systematic review to assess the efficacy and safety of CAPTEM in patients affected with NENs, with the aim to better clarify the role of this regimen in the therapeutic algorithm of NENs. Results A total of 42 articles and 1818 patients were included in our review. The overall disease control rate was 77% (range 43.5%-100%). The median progression free survival ranged from 4 to 38.5 months, while the median overall survival ranged from 8 to 103 months. Safety analysis showed an occurrence of G3-G4 toxicities in 16.4% of the entire population. The most common toxicities were hematological (27.2%), gastrointestinal (8.3%,) and cutaneous (3.2%). Conclusion This systematic review demonstrated that CAPTEM was an effective and relatively safe treatment for patients with advanced well-moderate differentiated NENs of gastroenteropancreatic, lung and unknown origin

Effects of caspofungin against Candida guilliermondii and Candida parapsilosis.

The in vitro activity of caspofungin (CAS) was investigated against 28 yeast isolates belonging to Candida albicans (n = 5), Candida guilliermondii (n = 10), and Candida parapsilosis (n = 13). CAS MICs obtained by broth dilution and Etest methods clearly showed a rank order of susceptibility to the echinocandin compound with C. albicans > C. parapsilosis > C. guilliermondii. Similarly, time-kill assays performed on selected isolates showed that CAS was fungistatic against C. albicans and C. parapsilosis, while it did not exert any activity against C. guilliermondii. In a murine model of systemic candidiasis, CAS given at doses as low as 1 mg/kg of body weight/day was effective at reducing the kidney burden of mice infected with either C. albicans or C. guilliermondii isolates. Depending on the isolate tested, mice infected with C. parapsilosis responded to CAS given at 1 and/or 5 mg/kg/day. However, the overall CFU reduction for C. guilliermondii and C. parapsilosis was approximately 100-fold less than that for C. albicans. Our study shows that CAS was active in experimental systemic candidiasis due to C. guilliermondii and C. parapsilosis, but this activity required relatively high drug dosages

THE "OLIVA ASCOLANA DEL PICENO DOP": PRODUCTION ASPECTS AND SELF-CONTROL PROGRAMS IN FACTORIES OF MARCHE REGION

The "Oliva Ascolana del Piceno" is a traditional product of the central part of Italy, which obtained the official designation of Denomination of Protected Origin (DOP) in 2006. This study analyzes the production aspects and the self-control programs in different tipologies of industries in Marche Region. The artisanal production is still used, but lately is growing up the industrial one. The industrial product shows an improvement of the healthy standards, but is not always able to ensure the preservation of the full taste and flavour. . The scrupulous respect of GMP and CCP in the handmade product can ensure, on the other hand, hight healthy standards and, at the same time, a better preservation of the organoleptic features

Evaluation of the Disk Diffusion Method Compared to the Microdilution Method in Susceptibility Testing of Anidulafungin against Filamentous Fungi

Susceptibility testing of anidulafungin (AFG) against 32 mold isolates showed an excellent correlation between disk diffusion (DD) and broth microdilution methods. Based on our data, a 2-microg disk of AFG and a 24-h reading time might represent the best parameters for AFG DD testing against filamentous fungi

Simulating the infrared sky with a Spritz

Current hydrodynamical and semi-empirical simulations of galaxy formation and evolution have difficulties in reproducing the number densities of IR-detected galaxies. Therefore, a versatile, phenomenological new simulation tool is necessary to reproduce current and predict future observations at IR wavelengths. In this work we generate simulated catalogues starting from the Herschel infrared luminosity functions of different galaxy populations, in order to consider in a consistent way different populations of galaxies and active galactic nuclei. We associated a spectral energy distribution and physical properties, such as stellar mass, star-formation-rate and AGN contribution, to each simulated galaxy using a broad set of empirical relations. We compare the resulting simulated galaxies, extracted up to z$=$10, with a broad set of observational relations. The Spectro-Photometric Realisations of Infrared-selected Targets at all-z (SPRITZ) simulation will allow us to obtain in a fully consistent way simulated observations for a broad set of current and future facilities with photometric capabilities as well as low-resolution IR spectroscopy, like the James Webb Space Telescope (JWST) or the Origin Space Telescope (OST). The derived simulated catalogue contains galaxies and active galactic nuclei that by construction reproduce the observed IR galaxy number density, but it is also in agreement with the observed number counts from UV to far-IR wavelengths, the observed stellar mass function, the star-formation-rate vs. stellar mass plane and the luminosity function from the radio to the X-ray. The proposed simulation is therefore ideal to make predictions for current and future facilities, in particular, but not limited to, those operating at IR wavelengths. The SPRITZ simulation will be publicly available.Comment: Accepted for publication in A&A, 32 pages, 30 figure

Simulating the infrared sky with a S PRITZ

Aims. Current hydrodynamical and semi-empirical simulations of galaxy formation and evolution have difficulties in reproducing the number densities of infrared-detected galaxies. Therefore, a phenomenological simulation tool that is new and versatile is necessary to reproduce current and predict future observations at infrared (IR) wavelengths. Methods. In this work we generate simulated catalogues starting from the Herschel IR luminosity functions of different galaxy populations to consider different populations of galaxies and active galactic nuclei (AGN) in a consistent way. We associated a spectral energy distribution and physical properties, such as stellar mass, star formation rate, and AGN contribution, with each simulated galaxy using a broad set of empirical relations. We compared the resulting simulated galaxies, extracted up to z = 10, with a broad set of observational relations. Results. Spectro-Photometric Realisations of IR-Selected Targets at all-z (SPRITZ) simulations allow us to obtain, in a fully consistent way, simulated observations for a broad set of current and future facilities with photometric capabilities as well as low-resolution IR spectroscopy, such as the James Webb Space Telescope (JWST) or the Origin Space Telescope (OST). The derived simulated catalogue contains galaxies and AGN that by construction reproduce the observed IR galaxy number density, but this catalogue also agrees with the observed number counts from UV to far-IR wavelengths, the observed stellar mass function, the star formation rate versus stellar mass plane, and the luminosity function from the radio to X-ray wavelengths. The proposed simulation is therefore ideal to make predictions for current and future facilities, in particular, but not limited to, those operating at IR wavelengths

Health-related quality of life in breast cancer patients treated with CDK4/6 inhibitors: a systematic review

Background: Evaluation of health-related quality of life (HR-QoL) among cancer patients has gained an increasing importance and is now a key determinant of anticancer treatments’ value. HR-QoL has been assessed in trials testing cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in breast cancer (BC), using various questionnaires at different timepoints. HR-QoL reports from BC patients treated with CDK4/6i in the real-world setting are also available. Methods: We systematically reviewed the literature, searching for full-length articles, and selected conference abstracts reporting data on HR-QoL in BC patients at any stage and of any molecular subtype treated with abemaciclib, palbociclib or ribociclib. Results: A total of 533 full-length articles and 143 abstracts were retrieved. After screening for eligibility, 38 records were included (31 clinical trials; 7 real-world reports). Assessment methods were heterogeneous across studies in terms of questionnaires, evaluation timepoints and endpoints. Overall, adding CDK4/6i to endocrine therapy did not worsen patients’ HR-QoL, with a positive trend towards pain improvement. Gastrointestinal scores (diarrhea, nausea and appetite loss) statistically favored the control arm among metastatic BC patients receiving abemaciclib, whereas they were superimposable in the early setting. The combination of palbociclib and endocrine therapy showed similar HR-QoL outcomes compared with endocrine therapy alone, but determined better scores compared with chemotherapy. HR-QoL was specifically assessed in premenopausal patients treated with ribociclib, showing similar scores compared with postmenopausal patients. Conclusions: Despite methodological heterogeneity does not allow a proper comparison, HR-QoL was generally maintained with CDK4/6i. However, differences between abemaciclib, palbociclib and ribociclib exist and mainly rely on the distinct safety profiles of the compounds. These differences should be acknowledged and taken into account in the clinical practice

Light depolarization effects in tip enhanced Raman spectroscopy of silicon (001) and gallium arsenide (001)

We report on the effects of light depolarization induced by sharp metallic tips in Tip-Enhanced Raman Spectroscopy (TERS). Experiments on Si(001) and GaAs(001) crystals show that the excitation field depolarization induces a selective enhancement of specific Raman modes, depending on their Raman tensor symmetry. A complete polarization analysis of the light backscattered from the tip confirms the TERS findings. The spatial confinement of the depolarization field is studied and its dependence on the excitation wavelength and power are explored

Discrete structure of ultrathin dielectric films and their surface optical properties

The boundary problem of linear classical optics about the interaction of electromagnetic radiation with a thin dielectric film has been solved under explicit consideration of its discrete structure. The main attention has been paid to the investigation of the near-zone optical response of dielectrics. The laws of reflection and refraction for discrete structures in the case of a regular atomic distribution are studied and the structure of evanescent harmonics induced by an external plane wave near the surface is investigated in details. It is shown by means of analytical and numerical calculations that due to the existence of the evanescent harmonics the laws of reflection and refraction at the distances from the surface less than two interatomic distances are principally different from the Fresnel laws. From the practical point of view the results of this work might be useful for the near-field optical microscopy of ultrahigh resolution.Comment: 25 pages, 16 figures, LaTeX2.09, to be published in Phys.Rev.