000162046 001__ 162046
000162046 005__ 20251017144644.0
000162046 0247_ $$2doi$$a10.1021/acsanm.5c01459
000162046 0248_ $$2sideral$$a144634
000162046 037__ $$aART-2025-144634
000162046 041__ $$aeng
000162046 100__ $$aRosso, Giada
000162046 245__ $$aRational design of EV-Mimicking nanoparticles with polarity-based recognition potential for advanced nanocarrier development
000162046 260__ $$c2025
000162046 5060_ $$aAccess copy available to the general public$$fUnrestricted
000162046 5203_ $$aExtracellular vesicles (EVs) are natural carriers that are essential for intracellular communication, delivering biomolecules with high efficiency and selectivity. Their application in a clinical setting has been limited, however, due to their complexity and heterogeneity, which hamper standardization in isolation procedures. A solution could be to engineer synthetic nanoparticles that are able to mimic the natural EV structure and function, which would lead to innovative therapeutic nanoplatforms with key advantages over traditional synthetic nanoparticles in terms of toxicity and efficacy. Here, we report an approach to designing, synthesizing, and characterizing lipid-coated nanoparticles engineered to replicate key biophysical surface properties of EVs relevant to cellular recognition and biointerface interactions. Three different lipidic mixtures were designed based on lipidomic data of prostate cancer-derived EVs, taking into consideration the mass percentage of both the lipid families and the fatty acids. Furthermore, breakable organosilica nanocapsules were employed as a functional core and coated with the lipidic mixtures to form eventual EV-mimicking nanocarriers (EV Mimics). Computational modeling of the lipid bilayer was employed to further optimize the lipid coverage of the organosilica nanocapsules. In addition to conventional characterization techniques, which assessed the matching of size and surface charge of EV Mimics and natural EVs, we used advanced single-particle characterization techniques, such as high-resolution flow cytometry and super-resolution microscopy, to assess coating efficacy, size distribution, and lipid polarity─a key parameter in cellular uptake and membrane interaction of EV Mimics. This multidisciplinary approach led to the discovery of a formulation (called “CE Mimic 3”, composed of Chol/SM/PE/PC/PS with respective mass ratios of 30/16.1/12.9/20.9/20.1) that closely reproduces the size, charge, lipid coating, and polarity of natural EVs, thus laying the groundwork for the development of EV-mimetic nanoplatforms for biomedical applications such as targeted delivery or biosensing.
000162046 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000162046 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000162046 700__ $$aVan Veen, Stijn M.A.
000162046 700__ $$0(orcid)0000-0001-8762-5457$$aSancho-Albero, María$$uUniversidad de Zaragoza
000162046 700__ $$aTamboia, Giulia
000162046 700__ $$aEmpereur-Mot, Charly
000162046 700__ $$aPerego, Claudio
000162046 700__ $$aKuipers, Marije E.
000162046 700__ $$aDumontel, Bianca
000162046 700__ $$aAjó, Alessandro
000162046 700__ $$aNolte-’t Hoen, Esther N.
000162046 700__ $$aPavan, Giovanni M.
000162046 700__ $$aCola, Luisa De
000162046 700__ $$aAlbertazzi, Lorenzo
000162046 700__ $$aCauda, Valentina
000162046 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química
000162046 773__ $$g8, 26 (2025), 13257-13273$$pACS appl. nano mater.$$tACS APPLIED NANO MATERIALS$$x2574-0970
000162046 8564_ $$s7246614$$uhttps://zaguan.unizar.es/record/162046/files/texto_completo.pdf$$yVersión publicada
000162046 8564_ $$s3472441$$uhttps://zaguan.unizar.es/record/162046/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000162046 909CO $$ooai:zaguan.unizar.es:162046$$particulos$$pdriver
000162046 951__ $$a2025-10-17-14:33:10
000162046 980__ $$aARTICLE