3D cellular spheroids as tools for understanding carboxylated quantum dot behavior in tumors

• Published in: Biochimica et biophysica acta. General subjects 2018-04, Vol.1862 (4), p.914-923
• Main Authors: Jarockyte, Greta, Dapkute, Dominyka, Karabanovas, Vitalijus, Daugmaudis, Justinas V., Ivanauskas, Feliksas, Rotomskis, Ricardas
• Format: Article
• Language: English
• Subjects: 3D spheroid cell culture; Accumulation; Animals; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cadmium Compounds - chemistry; Cadmium Compounds - metabolism; Carboxylic Acids - chemistry; Carboxylic Acids - metabolism; Cell Culture Techniques; Cell Line, Tumor; Cellular spheroids; Confocal microscopy; Distribution; Hanging drop; Human tumor xenografts; Humans; Mathematical model; MCF-7 Cells; Mice; Microscopy, Confocal; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - metabolism; NIH 3T3 Cells; Penetration; Quantum Dots; Selenium Compounds - chemistry; Selenium Compounds - metabolism; Spheroids, Cellular - chemistry; Spheroids, Cellular - metabolism; Sulfides - chemistry; Sulfides - metabolism; Transplantation, Heterologous; Zinc Compounds - chemistry; Zinc Compounds - metabolism
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.12.014

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. 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. 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. Penetration of negatively charged nanoparticles is limited not only in tumor tissue, but also in cellular spheroids. 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. [Display omitted] •CdSe/ZnS QDs accumulate in 3–4 cell layers from the surface of cellular spheroid.•QD penetration depth into spheroid depends on cells density, but not spheroid size.•CdSe/ZnS QDs penetration into in vivo tumor model is limited and heterogeneous.•Mathematical model of QDs distribution inside the spheroids was proposed.