Head-to-Head Comparison of the Penetration Efficiency of Lipid-Based Nanoparticles into Tumor Spheroids
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Head-to-Head Comparison of the Penetration Efficiency of Lipid-Based Nanoparticles into Tumor Spheroids. / Niora, Maria; Pedersbaek, Dennis; Munter, Rasmus; Weywadt, Matilda Felicia de Val; Farhangibarooji, Younes; Andresen, Thomas L.; Simonsen, Jens B.; Jauffred, Liselotte.
In: ACS Omega, Vol. 5, No. 33, 25.08.2020, p. 21162-21171.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Head-to-Head Comparison of the Penetration Efficiency of Lipid-Based Nanoparticles into Tumor Spheroids
AU - Niora, Maria
AU - Pedersbaek, Dennis
AU - Munter, Rasmus
AU - Weywadt, Matilda Felicia de Val
AU - Farhangibarooji, Younes
AU - Andresen, Thomas L.
AU - Simonsen, Jens B.
AU - Jauffred, Liselotte
PY - 2020/8/25
Y1 - 2020/8/25
N2 - 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.
AB - 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.
KW - HIGH-DENSITY-LIPOPROTEIN
KW - DRUG-DELIVERY SYSTEMS
KW - PARTICLE-SIZE
KW - LIPOSOMES
KW - PHARMACOKINETICS
KW - BIODISTRIBUTION
KW - ACCUMULATION
KW - MICROSCOPY
KW - STABILITY
KW - CARRIERS
U2 - 10.1021/acsomega.0c02879
DO - 10.1021/acsomega.0c02879
M3 - Journal article
C2 - 32875252
VL - 5
SP - 21162
EP - 21171
JO - ACS Omega
JF - ACS Omega
SN - 2470-1343
IS - 33
ER -
ID: 248807144