Accumulation and Distribution of Non-targeted and Anti-CD44-conjugated Quantum Dots in Distinct Phenotypes of Breast Cancer

Steponkienė, Simona; Dapkutė, Dominyka; Riekstiņa, Una; Rotomskis, Ričardas

doi:10.4172/2157-7439.1000341

Cited by 5 publications

(4 citation statements)

References 52 publications

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“…The cytotoxic effect of Au-MES NCs was more significant on MCF-7 cells than on MDA-MB-231 cells, along with higher intracellular ROS generation, which is in agreement with the results reported by other authors showing that MDA-MB-231 cells are more resistant to treatment and exhibit properties of cancer stem-like cells [ 70 , 71 ].…”

Section: Discussionsupporting

confidence: 91%

Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

Matulionytė

Dapkutė

Budenaite

et al. 2017

IJMS

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In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)-capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters.

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Section: Discussionsupporting

confidence: 91%

Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

Matulionytė

Dapkutė

Budenaite

et al. 2017

IJMS

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“…49,50 We previously showed that the antibody-QD complex not only recognizes its specific antigen, but also is engulfed inside the cells, while antibodies conjugated with commonly used organic fluorophore FITC remained on the cell membrane. 50 Although these results show promising potential of antibody-nanoparticle complexes to be used in both diagnostics and therapy, the success of such therapy is limited due to lack of tumor-specific antigens. 51 Ergo, nanoparticle transportation using cells that are naturally attracted to tumors emerged as a potential treatment method.…”

Section: Discussionmentioning

confidence: 99%

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Dapkutė¹,

Steponkienė²,

Bulotienė³

et al. 2017

IJN

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Purpose Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors. Such characteristics enable MSCs to be used in cellular hitchhiking of nanoparticles. In this study, MSCs extracted from the skin connective tissue were investigated as transporters of semiconductor nanocrystals quantum dots (QDs). Materials and methods Cytotoxicity of carboxylated CdSe/ZnS QDs was assessed by lactate dehydrogenase cell viability assay. Quantitative uptake of QDs was determined by flow cytometry; their intracellular localization was evaluated by confocal microscopy. In vitro tumor-tropic migration of skin-derived MSCs was verified by Transwell migration assay. For in vivo migration studies of QD-loaded MSCs, human breast tumor-bearing immunodeficient mice were used. Results QDs were found to be nontoxic to MSCs in concentrations no more than 16 nM. The uptake studies showed a rapid QD endocytosis followed by saturating effects after 6 h of incubation and intracellular localization in the perinuclear region. In vitro migration of MSCs toward MDA-MB-231 breast cancer cells and their conditioned medium was up to nine times greater than the migration toward noncancerous breast epithelial cells MCF-10A. In vivo, systemically administered QD-labeled MSCs were mainly located in the tumor and metastatic tissues, evading most healthy organs with the exception being blood clearance organs (spleen, kidneys, liver). Conclusion Skin-derived MSCs demonstrate applicability in cell-mediated delivery of nanoparticles. The findings presented in this study promise further development of a cell therapy and nanotechnology-based tool for early cancer diagnostics and therapy.

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“…There were successful attempts to use a similar quantum dot–chlorin e6 complex in photodynamic cancer therapy [15]. Another study has shown that QDs, conjugated with antibodies against CD44, a marker of cancer stem-like cells, can be selectively engulfed by breast cancer cells [16]. Such surface modifications increase the potential of QDs for the use in targeted cancer diagnostics and therapies.…”

Section: Introductionmentioning

confidence: 99%

Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery

Saulīte¹,

Dapkutė²,

Pleiko³

et al. 2017

Beilstein J. Nanotechnol.

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Nanotechnology-based drug design offers new possibilities for the use of nanoparticles in imaging and targeted therapy of tumours. Due to their tumour-homing ability, nano-engineered mesenchymal stem cells (MSCs) could be utilized as vectors to deliver diagnostic and therapeutic nanoparticles into a tumour. In the present study, uptake and functional effects of carboxyl-coated quantum dots QD655 were studied in human skin MSCs. The effect of QD on MSCs was examined using a cell viability assay, Ki67 expression analysis, and tri-lineage differentiation assay. The optimal conditions for QD uptake in MSCs were determined using flow cytometry. The QD uptake route in MSCs was examined via fluorescence imaging using endocytosis inhibitors for the micropinocytosis, phagocytosis, lipid-raft, clathrin- and caveolin-dependent endocytosis pathways. These data showed that QDs were efficiently accumulated in the cytoplasm of MSCs after incubation for 6 h. The main uptake route of QDs in skin MSCs was clathrin-mediated endocytosis. QDs were mainly localized in early endosomes after 6 h as well as in late endosomes and lysosomes after 24 h. QDs in concentrations ranging from 0.5 to 64 nM had no effect on cell viability and proliferation. The expression of MSC markers, CD73 and CD90, and hematopoietic markers, CD34 and CD45, as well as the ability to differentiate into adipocytes, chondrocytes, and osteocytes, were not altered in the presence of QDs. We observed a decrease in the QD signal from labelled MSCs over time that could partly reflect QD excretion. Altogether, these data suggest that QD-labelled MSCs could be used for targeted drug delivery studies.

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Accumulation and Distribution of Non-targeted and Anti-CD44-conjugated Quantum Dots in Distinct Phenotypes of Breast Cancer

Cited by 5 publications

References 52 publications

Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery

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