Rational Design of EV-Mimicking Nanoparticles with Polarity-Based Recognition Potential for Advanced Nanocarrier Development

Sep 21, 2026

Uploaded by Rowan

Extracellular vesicles (EVs) act as natural carriers for intracellular communication, yet clinical use is constrained by their complexity and heterogeneity, which hinders standardized isolation. An engineered alternative is proposed through synthetic nanoparticles that replicate EV structure and function, enabling therapeutic nanoplatforms with improved toxicity and efficacy. The work designs lipid-coated EV-mimicking nanocarriers using prostate-cancer EV lipidomic data, organosilica nanocapsules, and computational optimization of lipid bilayers. Advanced single-particle characterization, including high-resolution flow cytometry and super-resolution microscopy, evaluates size, charge, coating efficacy, and lipid polarity key for uptake and membrane interaction. A formulation (“CE Mimic 3”) reproduces the EV physicochemical features, supporting EV-mimetic platforms for targeted delivery and biosensing.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

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Abstract

Introduction

Nanomedicine and liposomes: advantages and clinical translation limits

Extracellular vesicles as natural nanocarriers

Cancer-derived EV tropism and targeting potential

Utrecht University Repository | Title | Rational Design of EV-Mimicking Nanoparticles with Polarity-Based
Recognition Potential for Advanced Nanocarrier Development | | --- | --- | | Authors | Rosso , Giada; Van Veen , Stijn M.A. ; Sancho-Albero , María; Tamboia , Giulia; Empereur-Mot , Charly; Perego , Claudio; Kuipers , Marije E. ; Dumontel , Bianca; Ajó , Alessandro; Nolte-’t Hoen , Esther N. | | Published in | ACS Applied Nano Materials | | Publication Date | 2025-07-04 | | Link | [https://dspace.library. uu. nl/handle/1874/477547](https://dspace.library. uu. nl/handle/1874/477547) | | Citation | Rosso , G , Van Veen , S M A , Sancho-Albero , M , Tamboia , G , Empereur-Mot , C , Perego , C , Kuipers , M E , Dumontel , B , Ajó , A , Nolte-’t Hoen , E N , Pavan , G M , Cola , L D , Albertazzi , L & Cauda , V 2025 , ' Rational Design of EV-Mimicking Nanoparticles with Polarity-Based Recognition Potential for Advanced Nanocarrier Development ' , ACS Applied Nano Materials , vol. 8 , no. 26 , pp. 13257-13273. [https://doi.org/10.1021/acsanm.5c01459](https://doi.org/10.1021/acsanm.5c01459) | | Versions / License | Publisher version | | Rights | [https://www. uu. nl/en/university-library/license-and-reuse-conditions](https://www. uu. nl/en/university-library/license-and-reuse-conditions) | This article is licensed under CC-BY 4.0 [www.acsanm.org](www.acsanm.org) Article Rational Design of EV-Mimicking Nanoparticles with Polarity-Based Recognition Potential for Advanced Nanocarrier Development Giada Rosso,○ Stijn M.A. Van Veen,○ María Sancho-Albero, Giulia Tamboia, Charly Empereur-Mot, Claudio Perego, Marije E. Kuipers, Bianca Dumontel, Alessandro Ajó, Esther N. Nolte-’t Hoen, Giovanni M. Pavan, Luisa De Cola, Lorenzo Albertazzi, * and Valentina Cauda * Cite This: ACS Appl. Nano Mater. 2025, 8, 13257−13273 Read Online Downloaded via 77.16 1.2 1 1.187 on July 10, 2025 at 13:07:44 (UTC) . See [https://pubs.acs.org/sharingguidelines](https://pubs.acs.org/sharingguidelines) for options on how to legitimately share published articles. ACCESS Metrics & More Article Recommendations *sı Supporting Information ABSTRACT: Extracellular 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 formulat

FAQs

Why are extracellular vesicles (EVs) difficult to standardize for clinical use?

EVs are complex and heterogeneous, which complicates isolation procedures and limits standardization for clinical applications.

What is the core strategy used to create EV-mimicking nanocarriers?

Lipid-coated nanoparticles are engineered to replicate EV biophysical surface properties, using lipidomic data to design lipid mixtures and coating organosilica nanocapsules to form EV mimics.

How are EV mimic performance and lipid polarity evaluated?

Size and surface charge matching are assessed alongside advanced single-particle techniques such as high-resolution flow cytometry and super-resolution microscopy to quantify coating efficacy, size distribution, and lipid polarity relevant to cellular uptake and membrane interaction.

Sep 21, 2026

Uploaded by Rowan