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NP___spheres_preprint-3.pdf (9.25 MB)

Head-to-head comparison of the penetration efficiency of lipid-based nanoparticles in a 3D tumor spheroid model

preprint
submitted on 16.04.2020, 10:09 and posted on 20.04.2020, 06:13 by Maria Niora, Dennis Pedersbæk, Rasmus Mikkel Münter Lassen, Matilda Felicia de Val Weywadt, Thomas Lars Andresen, Jens Bæk Simonsen, Liselotte Jauffred

Most tumor-targeted drug delivery systems must overcome a large variety of physiological barriers before reaching the tumor site and diffuse through the tight network of tumor cells. Many studies focus on optimizing the first part, the accumulation of drug carriers at the tumor site, ignoring the penetration efficiency, i.e., a measure of the ability of a drug delivery system to overcome tumor surface adherence and uptake. We used 3D tumor spheroids in combination with light-sheet fluorescence microscopy in a head-to-head comparison of a variety of commonly used lipid-based nanoparticles, including liposomes, PEGylated liposomes, lipoplexes and reconstituted high-density lipoproteins (rHDL). Whilst PEGylation of liposomes only had minor effects on the penetration efficiency, we show that lipoplexes mainly associated to the periphery of tumor spheroids, possibly due to their positive surface charge leading to fusion with the cells at the spheroid surface or aggregation. Surprisingly, the rHDL showed significantly higher penetration efficiency and high accumulation inside the spheroid. While these findings indeed could be relevant when designing novel drug delivery systems based on lipid-based nanoparticles, we stress that the used platform and detailed image analysis is a versatile tool for in vitro studies of the penetration efficiency of nanoparticles in tumors.


Funding

DNRF116

History

Email Address of Submitting Author

jauffred@nbi.dk

Institution

University of Copenhagen

Country

Denmark

ORCID For Submitting Author

0000-0002-2223-9464

Declaration of Conflict of Interest

No conflicts of interest.

Exports