High toxicity, poor selectivity, and severe side effects are major drawbacks of anticancer drugs. Various drug delivery systems could be proposed to overcome these limitations. The aim of this study was to fabricate polysaccharide microcontainers (MCs) loaded with thymoquinone (TQ) by a one-step ultrasonication technique and to study their cellular uptake and cytotoxicity in vitro. Two MC fractions with a mean size of 500 nm (MC-0.5) and 2 μM (MC-2) were prepared and characterized. Uptake of the MCs by mouse melanoma M-3 cells was evaluated in both 2D (monolayer culture) and 3D (multicellular tumor spheroids) models by confocal microscopy, flow cytometry, and fluorimetry. The higher cytotoxicity of the TQ-MC-0.5 sample than the TQ-MC-2 fraction was in good correlation with higher MC-0.5 accumulation in the cells. The MC-0.5 beads were more promising than the MC-2 particles because of a higher cellular uptake in both 2D and 3D models, an enhanced antitumor effect, and a lower nonspecific toxicity.

In lymphocytes of donors studied in this work chromosome 2 appears to be consistently less sensitive to protons and heavy ions than chromosomes 8 and 14. Complex aberrations appear to be a potential marker of radiation quality.

Purpose: To investigate by FISH the distribution of radiation-induced chromosomal aberrations in chromosomes 2, 8 and 14 of 6 donors. Methods: Irradiation of blood from 6 healthy donors (4 male and 2 female) was performed at the accelerators at the Joint Institute for Nuclear Research in Dubna (Russia). Whole blood samples were irradiation with 3 Gy of protons (Phasotron), 3 Gy of 12 C-ions (Nuclotron), 4 Gy of 7 Li-ions and 3Gy of 11 B-ions (Cyclotron U400M). At the position of the samples the beams energy and LET values were following: protons -170 MeV/n and LET ≈ 0.5 keV/µm; 12 C -480 MeV/n and LET = 10.6 keV/µm; 7 Li -30 MeV/n and LET ≈ 20 keV/µm; 11 B -32 MeV/n and LET ≈ 55 keV/µm. Chromosome aberrations were analyzed in prematurely condensed G2-cells harvested after 48 in culture using calyculin A. Chromosomes 2, 8 and 14 were painted in different colors and aberrations scored with the help of an image-analysis system. Results: Chromosome 2 was generally less sensitive than expected on the basis of its DNA content. A higher than expected frequency of exchanges was found in chromosome 8, however, variable results were obtained for stable and unstable aberrations. The translocation frequency was higher and dicentric frequency was lower then expected. Chromosome 14 revealed the opposite tendency: for stable exchanges we found a lower sensitivity whereas the frequency of unstable exchanges was higher then expected. Generally, chromosome 14 was found to be less radiosensitive than expected. Conclusion: Chromosome 2 appears to be less sensitive to protons as well as to heavy ions than chromosomes 8 and 14. This result is in line with recent results of a study on the sensitivity of chromosomes 2, 8 and 14 to gamma rays.

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