Related Experiment Video
Updated: Dec 10, 2025
Establishing 3-Dimensional Spheroids from Patient-Derived Tumor Samples and Evaluating their Sensitivity to Drugs
Published on: December 16, 2022
Head-to-Head Comparison of the Penetration Efficiency of Lipid-Based Nanoparticles into Tumor Spheroids
Maria Niora1, Dennis Pedersbæk2, Rasmus Münter2
1The Niels Bohr Institute, University of Copenhagen, 2100 København, Denmark.
Abstract:
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 three-dimensional (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 are mainly associated with 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 the detailed image analysis are a versatile tool for in vitro studies of the penetration efficiency of nanoparticles in tumors.
Insights
Reconstituted high-density lipoproteins (rHDL) show superior tumor penetration compared to other lipid nanoparticles. This study highlights rHDL
Area of Science:
- Nanomedicine
- Biotechnology
- Cancer Research
Background:
- Tumor-targeted drug delivery faces challenges with physiological barriers and tumor cell penetration.
- Optimizing nanoparticle accumulation at tumor sites often neglects penetration efficiency.
- Effective drug delivery requires overcoming tumor surface adherence and cellular uptake.
Purpose of the Study:
- To compare the penetration efficiency of various lipid-based nanoparticles in a 3D tumor model.
- To evaluate the impact of nanoparticle properties on tumor penetration.
- To introduce a versatile platform for assessing nanoparticle penetration in vitro.
Main Methods:
- Utilized three-dimensional (3D) tumor spheroids as an in vitro tumor model.
- Employed light-sheet fluorescence microscopy for high-resolution imaging.
- Conducted a head-to-head comparison of liposomes, PEGylated liposomes, lipoplexes, and reconstituted high-density lipoproteins (rHDL).
Main Results:
- PEGylation of liposomes had minimal impact on penetration efficiency.
- Lipoplexes showed peripheral association with spheroids, likely due to surface charge and aggregation.
- Reconstituted high-density lipoproteins (rHDL) demonstrated significantly higher penetration efficiency and accumulation within spheroids.
Conclusions:
- Reconstituted high-density lipoproteins (rHDL) are promising candidates for enhanced tumor drug delivery due to superior penetration.
- Nanoparticle surface properties, like charge, significantly influence tumor penetration.
- The 3D spheroid model with light-sheet microscopy is a valuable tool for evaluating nanoparticle penetration efficiency in cancer research.
