Surface modification of extracellular vesicles with polyoxazolines to enhance their plasma stability and tumor accumulation.

Extracellular vesicles (EVs) are future promising therapeutics, but their instability in vivo after administration remains an important barrier to their further development. Many groups evaluated EV surface modification strategies to add a targeting group with the aim of controlling EV biodistribution. Conversely, fewer groups focused on their stabilization to obtain "stealth" allogenic EVs. Modulating their stabilization and biodistribution is an essential prerequisite for their development as nano-therapeutics. Here, we explored polyoxazolines with lipid anchors association to the EV membrane (POxylation as an alternative to PEGylation) to stabilize EVs in plasma and control their biodistribution, while preserving their native properties. We found that this modification maintained and seemed to potentiate the immunomodulatory properties of EVs derived from mesenchymal stem/stromal cells (MSC). Using a radiolabeling protocol to track EVs at a therapeutically relevant concentration in vivo, we demonstrated that POxylation is a promising option to stabilize EVs in plasma because it increased EV half-life by 6 fold at 6 h post-injection. Moreover, EV accumulation in tumors was higher after POxylation than after PEGylation.

Knowledge and participation of general practitioners in cervical cancer screening: survey in a French pilot area.

BACKGROUND: Eighteen months after the beginning of a pilot cervical cancer screening program in a French district of 484,770 inhabitants, a survey was performed among general practitioners (GP). The aim was to assess their knowledge of the screening policy, the factors related to their participation, the difficulties they encounter and their training needs. METHODS: A random sample of 168 GPs was taken from a medical association file. Eighty-seven percent of the physicians agreed to be interviewed by phone. The questionnaire was standardized and made up of open questions. RESULTS: On the whole, screening policy was not well known to the GPs: 58 percent believed screening had to begin before age 21 and could be discontinued before age 61. Sixty percent of GPs declared that they provided women with written information, and 49 percent that they offered Pap smears to all women. Seventy-nine percent said that they took Pap smears, but 39 percent claimed they had difficulty mainly due to women's reluctance or to technical problems. Few GPs expressed training needs. Reported difficulties and expressed need for training increased with the physician's age. GP concern for public health activities increased their participation in the campaign. CONCLUSION: Pilot programs have to implement measures which can help GPs to deal with community care and screening activities since GP involvement is one of the essential conditions of successful organized screening.