Greta Jarockyte1, Dominyka Dapkute1, Vitalijus Karabanovas2, Justinas V Daugmaudis3, Feliksas Ivanauskas3, Ricardas Rotomskis4. 1. Biomedical Physics Laboratory, National Cancer Institute, P. Baublio 3B, LT08406 Vilnius, Lithuania; Life Science Center, Vilnius University, Sauletekio ave. 7, LT-10257 Vilnius, Lithuania. 2. Biomedical Physics Laboratory, National Cancer Institute, P. Baublio 3B, LT08406 Vilnius, Lithuania; Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, Sauletekio ave. 11, LT-10223 Vilnius, Lithuania. 3. Faculty of Mathematics and Informatics, Vilnius University, Naugarduko 24, LT-03225 Vilnius, Lithuania. 4. Biomedical Physics Laboratory, National Cancer Institute, P. Baublio 3B, LT08406 Vilnius, Lithuania; Biophotonics group of Laser Research Centre, Vilnius University, Sauletekio ave 9, c.3, LT-10222 Vilnius, Lithuania. Electronic address: ricardas.rotomskis@nvi.lt.
Abstract
BACKGROUND: Monolayer cell cultures have been considered the most suitable technique for in vivo cellular experiments. However, a lot of cellular functions and responses that are present in natural tissues are lost in two-dimensional cell cultures. In this context, nanoparticle accumulation data presented in literature are often not accurate enough to predict behavior of nanoparticles in vivo. Cellular spheroids show a higher degree of morphological and functional similarity to the tissues. METHODS: Accumulation and distribution of carboxylated CdSe/ZnS quantum dots (QDs), chosen as model nanoparticles, was investigated in cellular spheroids composed of different phenotype mammalian cells. The findings were compared with the results obtained in in vivo experiments with human tumor xenografts in immunodeficient mice. The diffusive transport model was used for theoretical nanoparticles distribution estimation. RESULTS: QDs were accumulated only in cells, which were localized in the periphery of cellular spheroids. CdSe/ZnS QDs were shown to be stable and inert; they did not have any side-effects for cellular spheroids formation. Penetration of QDs in both cellular spheroids and in vivo tumor model was limited. The mathematical model confirmed the experimental results: nanoparticles penetrated only 25μm into cellular spheroids after 24h of incubation. CONCLUSIONS: Penetration of negatively charged nanoparticles is limited not only in tumor tissue, but also in cellular spheroids. GENERAL SIGNIFICANCE: The results presented in this paper show the superior applicability of cellular spheroids to cell monolayers in the studies of the antitumor effect and penetration of nanomedicines.
BACKGROUND: Monolayer cell cultures have been considered the most suitable technique for in vivo cellular experiments. However, a lot of cellular functions and responses that are present in natural tissues are lost in two-dimensional cell cultures. In this context, nanoparticle accumulation data presented in literature are often not accurate enough to predict behavior of nanoparticles in vivo. Cellular spheroids show a higher degree of morphological and functional similarity to the tissues. METHODS: Accumulation and distribution of carboxylated CdSe/ZnS quantum dots (QDs), chosen as model nanoparticles, was investigated in cellular spheroids composed of different phenotype mammalian cells. The findings were compared with the results obtained in in vivo experiments with humantumor xenografts in immunodeficientmice. The diffusive transport model was used for theoretical nanoparticles distribution estimation. RESULTS: QDs were accumulated only in cells, which were localized in the periphery of cellular spheroids. CdSe/ZnS QDs were shown to be stable and inert; they did not have any side-effects for cellular spheroids formation. Penetration of QDs in both cellular spheroids and in vivo tumor model was limited. The mathematical model confirmed the experimental results: nanoparticles penetrated only 25μm into cellular spheroids after 24h of incubation. CONCLUSIONS: Penetration of negatively charged nanoparticles is limited not only in tumor tissue, but also in cellular spheroids. GENERAL SIGNIFICANCE: The results presented in this paper show the superior applicability of cellular spheroids to cell monolayers in the studies of the antitumor effect and penetration of nanomedicines.
Authors: W Souza; S G Piperni; P Laviola; A L Rossi; Maria Isabel D Rossi; Bráulio S Archanjo; P E Leite; M H Fernandes; L A Rocha; J M Granjeiro; A R Ribeiro Journal: Sci Rep Date: 2019-06-27 Impact factor: 4.379
Authors: Jana Fleddermann; Julia Susewind; Henrike Peuschel; Marcus Koch; Isabella Tavernaro; Annette Kraegeloh Journal: Int J Nanomedicine Date: 2019-02-22