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Enantioselective interaction of chiral semiconductor nanocrystals and tumor cells

Name
Irina
Surname
Martynenko
Scientific organization
ITMO University
Academic degree
PhD
Position
research fellow
Scientific discipline
Physics & Astronomy
Topic
Enantioselective interaction of chiral semiconductor nanocrystals and tumor cells
Abstract
The aim of study was to investigate the enantioselective interaction of semiconductor nanocrystals of different shapes with living tumor cells. Using methods of confocal fluorescence microscopy and FLIM we investigated optical properties, cellular uptake and cytotoxicity of chiral nanocrystals against A-549 and Ehrlich Ascite carcinoma cell lines. We demonstrated evident enantioselective cellular uptake and cytotoxicity of chiral nanocrystals while the intracellular optical properties of nanocrystals did not depend on their chirality.
Keywords
quantum dots, quantum rods, quantum tetra-pods, cytotoxicity, cellular uptake, fluorescence spectroscopy, FLIM
Summary

Chirality is a common property of the most part of active biological molecules that provide their stereospecific interactions with environment. Many properties such as the ability to penetrate into cells, enzymatic activity and toxicity are strongly dependent on chirality of substances.1

A creation of man-made chiral inorganic structures is a hot trend in nanotechnology today. An acquisition by nanostructure chiral properties should lead to significant changing in their interactions with biomolecules. It opens new possibilities to realize stereospecific interactions of nanostructures in biological environment.2

Semiconductor nanocrystals (NCs)3 is a vivid specimen of man-made inorganic nanoparticles that can be widely used in many fields of biological studies. 4 Recent studies demonstrated for the first time the induction of chiroptical activity in NCs.2-5 NC s are able to obtain chirality as the result of attaching the chiral molecules to the NC surface.2

To fully understand the interactions between NC s and living cells in order to develop nontoxic and biocompatible NC s for clinical use the impact on living organisms of the chirality of NC s should be investigated. Different chiral properties of NC s may determine their ability to interact with other biomolecules and thereby modulate a range of downstream processes in living cells. In5 was demonstrated differential NC cell toxicity associated with the chirality of glutathione coating of CdTe quantum dots (QDs). QDs coated with D-glutathione, the nonbiologically active form of glutathione, showed less cytotoxicity than L-glutathione-coated QDs.

The aim of study was to investigate the enantioselective interaction of semiconductor nanocrystals of different shapes and living tumor cells. Using methods of confocal fluorescence microscopy and FLIM we investigated optical properties, cellular uptake and cytotoxicity of chiral nanocrystals against A-549 and Ehrlich Ascite carcinoma cell lines.

Hydrophobic trioctylphosphine oxide (TOPO) capped CdSe/ZnS spherical quantum dots, dots in rods and dots in tetrapods were prepared according to methods described in.6 Chiral NCs were obtained from hydrophobic CdSe/ZnS NCs by the method of post-synthesis ligand exchange using D- and L-cysteine (Cys) as chiral ligands.

Circular dichroism spectra of the D- and L-cysteine capped NC demonstrated a pronounced antiphase optical dichroism signal in the spectral region of intrinsic NC absorption

Cell toxicity and intracellular accumulation of NCs were investigated on A-549 and Ehrlich Ascite carcinoma cells by high content screening and confocal PL microscopy respectively.

Optical properties of NCs inside A-549 and Ehrlich Ascite carcinoma cells were studied by confocal PL microscopy and time-resolved PL microscopy to obtain PL intensity and PL lifetimes data of NCs inside cells.

It was shown that chirality of NCs did not influence on their optical characteristics inside cells, but had crucial role in the NC cytotoxicity and cellular uptake. It was demonstrated that L-Cys NCs had higher cellular accumulation in the case of Ehrlich Ascite carcinoma cells while D-Cys NCs were more biologically active in A-549 cells. Cytotoxicity of chiral quantum dots against Ehrlich Ascite carcinoma cells did not exceed 10% in the concentration region 1–20 μmol L−1 of QDs. In this case, L-Cys QDs had slightly higher cytotoxicity than D-Cys QDs. However, D-Cys NCs had more pronounced cytotoxicity than L-Cys NCs against A-549 cells. The establishment of exact mechanisms of NP biological effects is our ongoing research.

We believe that this finding may lay the groundwork for novel approaches to controlling the biological properties and behavior of man-made chiral nanomaterials in living cells.

References:

1.          Cintas, P., Chirality of living systems: a helping hand from crystals and oligopeptides. Angewandte Chemie (International ed. in English) 2002, 41 (7), 1139-45.

2.          Xia, Y.; Zhou, Y.; Tang, Z., Chiral inorganic nanoparticles: origin, optical properties and bioapplications. Nanoscale 2011, 3 (4), 1374-1382.

3.          Ėfros, A. L.; Lockwood, D. J.; Tsybeskov, L., Semiconductor Nanocrystals: From Basic Principles to Applications. Springer: USA, 2003.

4.          (a) Medintz, I. L.; Uyeda, H. T.; Goldman, E. R.; Mattoussi, H., Quantum dot bioconjugates for imaging, labelling and sensing. Nature materials 2005, 4 (6), 435-446; (b) Maslov, V.; Orlova, A.; Baranov, A., Combination Therapy: Complexing of QDs with tetrapyrrols and other dyes. In Photosensitizers in Medicine, Environment, and Security, Springer-Verlag, Ed. Springer: USA, 2012; (c) Li, L.; Zhao, J. F.; Won, N.; Jin, H.; Kim, S.; Chen, J. Y., Quantum dot-aluminum phthalocyanine conjugates perform photodynamic reactions to kill cancer cells via fluorescence resonance energy transfer. Nanoscale research letters 2012, 7 (1), 386.

5.          Li, Y.; Zhou, Y.; Wang, H.-Y.; Perrett, S.; Zhao, Y.; Tang, Z.; Nie, G., Chirality of Glutathione Surface Coating Affects the Cytotoxicity of Quantum Dots. Angewandte Chemie International Edition 2011, 50 (26), 5860-5864.

6.          (a) Talapin, D. V.; Rogach, A. L.; Kornowski, A.; Haase, M.; Weller, H., Highly Luminescent Monodisperse CdSe and CdSe/ZnS Nanocrystals Synthesized in a Hexadecylamine−Trioctylphosphine Oxide−Trioctylphospine Mixture. Nano Letters 2001, 1 (4), 207-211; (b) Govan, J. E.; Jan, E.; Querejeta, A.; Kotov, N. A.; Gun'ko, Y. K., Chiral luminescent CdS nano-tetrapods. Chemical Communications 2010, 46 (33), 6072-6074; (c) Artemyev, M.; Möller, B.; Woggon, U., Unidirectional Alignment of CdSe Nanorods. Nano Letters 2003, 3 (4), 509-512.