Targeted chitosan nanobubbles as a strategy to down-regulate microRNA-17 into B-cell lymphoma models

IntroductionMicroRNAs represent interesting targets for new therapies because their altered expression influences tumor development and progression. miR-17 is a prototype of onco-miRNA, known to be overexpressed in B-cell non-Hodgkin lymphoma (B-NHL) with peculiar clinic-biological features. AntagomiR molecules have been largely studied to repress the regulatory functions of up-regulated onco-miRNAs, but their clinical use is mainly limited by their rapid degradation, kidney elimination and poor cellular uptake when injected as naked oligonucleotides.MethodsTo overcome these problems, we exploited CD20 targeted chitosan nanobubbles (NBs) for a preferential and safe delivery of antagomiR17 to B-NHL cells.ResultsPositively charged 400 nm-sized nanobubbles (NBs) represent a stable and effective nanoplatform for antagomiR encapsulation and specific release into B-NHL cells. NBs rapidly accumulated in tumor microenvironment, but only those conjugated with a targeting system (antiCD20 antibodies) were internalized into B-NHL cells, releasing antagomiR17 in the cytoplasm, both in vitro and in vivo. The result is the down-regulation of miR-17 level and the reduction in tumor burden in a human-mouse B-NHL model, without any documented side effects.DiscussionAnti-CD20 targeted NBs investigated in this study showed physico-chemical and stability properties suitable for antagomiR17 delivery in vivo and represent a useful nanoplatform to address B-cell malignancies or other cancers through the modification of their surface with specific targeting antibodies

Mutations in the 3' untranslated region (3' UTR) of NOTCH1 are associated with low CD20 expression levels in chronic lymphocytic leukemia

20letteropenopenBittolo, Tamara; Pozzo, Federico; Bomben, Riccardo; D'Agaro, Tiziana; Bravin, Vanessa; Bulian, Pietro; Rossi, Francesca Maria; Zucchetto, Antonella; Degan, Massimo; Macor, Paolo; D'Arena, Giovanni; Chiarenza, Annalisa; Zaja, Francesco; Pozzato, Gabriele; Di Raimondo, Francesco; Rossi, Davide; Gaidano, Gianluca; Del Poeta, Giovanni; Gattei, Valter; Dal Bo, MicheleBittolo, Tamara; Pozzo, Federico; Bomben, Riccardo; D'Agaro, Tiziana; Bravin, Vanessa; Bulian, Pietro; Rossi, Francesca Maria; Zucchetto, Antonella; Degan, Massimo; Macor, Paolo; D'Arena, Giovanni; Chiarenza, Annalisa; Zaja, Francesco; Pozzato, Gabriele; Di Raimondo, Francesco; Rossi, Davide; Gaidano, Gianluca; Del Poeta, Giovanni; Gattei, Valter; Dal Bo, Michel

Spotlight on measles in Italy: why outbreaks of a vaccine-preventable infection continue in the 21st century

Measles is a serious infectious disease that can lead to significant morbidity and mortality. Remarkable progress has been made through measles vaccination in reducing the number of people dying from measles. In the last years, concerns about the safety of vaccines have led to decline in immunization coverage rates and new outbreaks of measles in many European countries, including Italy. We believe that it is important to reinforce the message that measles vaccine is safe and highly effective through appropriate information campaigns and public awareness

Tracking the progressive spread of the SARS-CoV-2 Omicron variant in Italy, December 2021 to January 2022

The SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021.AimTo comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level.MethodsWe analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility.ResultsOmicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9-80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7-3.3 days. As of 17 January 2022, Delta variant represented < 6% of cases. During the Omicron expansion in December 2021, the estimated mean net reproduction numbers respectively rose from 1.15 to a maximum of 1.83 for symptomatic cases and from 1.14 to 1.36 for hospitalised cases, while remaining relatively stable, between 0.93 and 1.21, for cases needing intensive care. Despite a reduction in relative proportion, Delta infections increased in absolute terms throughout December contributing to an increase in hospitalisations. A significant reproduction numbers' decline was found after mid-January, with average estimates dropping below 1 between 10 and 16 January 2022.ConclusionEstimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at population level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection