Efficient subcellular targeting to the cell nucleus of Quantum Dots densely decorated with a nuclear localization sequence peptide
Abstract
Organelle-targeted drug delivery can enhance the efficiency of the intracellularly acting drugs and reduce their toxicity. We generated core-shell type CdSe-ZnS quantum dots (QDs) densely decorated with NLS peptidic targeting residues using a 3-stage decoration approach and investigated their endocytosis and nuclear targeting efficiencies. The diameter of the generated QDs increased following the individual decoration stages (16.3, 18.9, and 21.9 nm), the ζ-potential became less negative (-33.2, -17.5, and -11.9 mV), and characteristic changes appeared in the FTIR spectra following decoration with the linker and NLS peptides. Quantitative analysis of the last decoration stage revealed that 37.9% and 33.2% of the alkyne-modified NLS groups that were added to the reaction mix became covalently attached or adsorbed to the QDs surface, respectively. These numbers correspond to 63.6 and 55.7 peptides conjugated or adsorbed to a single QD (the surface density of 42 and 37 conjugated and adsorbed peptides per 1000 nm(2) of the QDs surface), which is higher than in the majority of previous studies that reported decoration efficiencies of formulations intended for nuclear-targeted drug delivery. QDs decorated with NLS peptides undergo more efficient endocytosis, as compared to other investigated QDs formulations, and accumulated to a higher extent in the cell nucleus or in close vicinity to it (11.9%, 14.6%, and 56.1% of the QDs endocytosed by an average cell for the QD-COOH, QD-azide, and QD-NLS formulations, respectively). We conclude that dense decoration of QDs with NLS residues increased their endocytosis and led to their nuclear targeting (preferential accumulation in the cells nuclei or in close vicinity to them). The experimental system and research tools that were used in this study allow quantitative investigation of the mechanisms that govern the QDs nuclear targeting and their dependence on the formulation properties. These findings will contribute to the development of subcellularly targeted DDSs that will deliver specific drugs to the nuclei of the target cells and will enhance efficacy and reduce toxicity of these drugs.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NLSs have been introduced into vectors to facilitate transportation to nucleus.
“Inspired by the active transportation process of proteins to nucleus, nuclear localization sequences (NLSs) have been introduced into the vectors to facilitate transportation to nucleus [195–197].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [197]
Cites
Murray, C. B., Norris, D. J., & Bawendi, M. G. (1993) · Journal of the American Chemical Society · doi:10.1021/ja00072a025 · Cited by 9,334 · see citing works
Experimental Determination of the Extinction Coefficient of CdTe, CdSe, and CdS Nanocrystals
Yu, W. W., Qu, L., Guo, W., & Peng, X. (2003) · Chemistry of Materials · doi:10.1021/cm034081k · Cited by 4,997 · see citing works
Multifunctional Gold Nanoparticle−Peptide Complexes for Nuclear Targeting
Tkachenko, A. G., Xie, H., Coleman, D. M., Glomm, W. R., Ryan, J. A., Anderson, M. F., Franzen, S., & Feldheim, D. L. (2003) · Journal of the American Chemical Society · doi:10.1021/ja0296935 · Cited by 795 · see citing works
Nuclear Pore Complex Is Able to Transport Macromolecules with Diameters of ∼39 nm
Panté, N., & Kann, M. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-06-0308 · Cited by 778 · see citing works
RECENT APPROACHES TO INTRACELLULAR DELIVERY OF DRUGS AND DNA AND ORGANELLE TARGETING
Torchilin, V. P. (2006) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.8.061505.095735 · Cited by 542 · see citing works
Chen, F., & Gerion, D. (2004) · Nano Letters · doi:10.1021/nl049170q · Cited by 492 · see citing works
Cell Penetrating Peptides: Intracellular Pathways and Pharmaceutical Perspectives
Patel, L. N., Zaro, J. L., & Shen, W. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9303-7 · Cited by 426 · see citing works
The nuclear pore complex: nucleocytoplasmic transport and beyond
Fahrenkrog, B., & Aebi, U. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1230 · Cited by 421 · see citing works
Proton-Sponge Coated Quantum Dots for siRNA Delivery and Intracellular Imaging
Yezhelyev, M. V., Qi, L., O'Regan, R. M., Nie, S., & Gao, X. (2008) · Journal of the American Chemical Society · doi:10.1021/ja800086u · Cited by 406 · see citing works
Understanding nanoparticle cellular entry: A physicochemical perspective
Beddoes, C. M., Case, C. P., & Briscoe, W. H. (2015) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2015.01.007 · Cited by 337 · see citing works
Duncan, R., & Richardson, S. C. W. (2012) · Molecular Pharmaceutics · doi:10.1021/mp300293n · Cited by 333 · see citing works
Nanopreparations for organelle-specific delivery in cancer
Biswas, S., & Torchilin, V. P. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.11.004 · Cited by 292 · see citing works
Ding, H., & Ma, Y. (2014) · Small · doi:10.1002/smll.201401943 · Cited by 259 · see citing works
Pan, L., Liu, J., He, Q., Wang, L., & Shi, J. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2012.12.040 · Cited by 252 · see citing works
Targeted delivery to the nucleus☆
Pouton, C. W., Wagstaff, K. M., ROTH, D., Moseley, G. W., & Jans, D. A. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.06.010 · Cited by 246 · see citing works
Intracellular trafficking of nuclear localization signal conjugated nanoparticles for cancer therapy
Misra, R., & Sahoo, S. K. (2009) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2009.11.010 · Cited by 218 · see citing works
Polymers and nanoparticles: Intelligent tools for intracellular targeting?
Breunig, M., Bauer, S., & Göpferich, A. M. (2007) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2007.06.010 · Cited by 214 · see citing works
Quantum Dots Targeted to the Assigned Organelle in Living Cells
Hoshino, A., Fujioka, K., Oku, T., et al. (2004) · Microbiology and Immunology · doi:10.1111/j.1348-0421.2004.tb03621.x · Cited by 210 · see citing works
The nuclear pore complex: a jack of all trades?
Fahrenkrog, B., Köser, J., & Aebi, U. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.02.006 · Cited by 133 · see citing works
Mechanisms and Signals for the Nuclear Import of Proteins
Freitas, N., & Cunha, C. V. (2009) · Current Genomics · doi:10.2174/138920209789503941 · Cited by 122 · see citing works
Sneh-Edri, H., Likhtenshtein, D., & Stepensky, D. (2011) · Molecular Pharmaceutics · doi:10.1021/mp200198c · Cited by 121 · see citing works
Self-citationChakraborty, A., & Jana, N. R. (2015) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.5b01739 · Cited by 106 · see citing works
Tammam, S. N., Azzazy, H. M. E.-S., Breitinger, H., & Lamprecht, A. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00478 · Cited by 97 · see citing works
Tachibana, R., Harashima, H., Shono, M., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9460 · Cited by 82 · see citing works
Axial resolution of confocal fluorescence microscopy
Sheppard, C. J. R. (1989) · Journal of Microscopy · doi:10.1111/j.1365-2818.1989.tb00586.x · Cited by 59 · see citing works
Nuclear drug delivery to target tumour cells
Wagstaff, K. M., & Jans, D. A. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.06.069 · Cited by 56 · see citing works
The Role of Ligand Density and Size in Mediating Quantum Dot Nuclear Transport
Tang, P. S., Sathiamoorthy, S., Lustig, L. C., Ponzielli, R., Inamoto, I., Penn, L. Z., Shin, J. A., & Chan, W. C. W. (2014) · Small · doi:10.1002/smll.201401056 · Cited by 46 · see citing works
Maity, A. R., & Stepensky, D. (2015) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2015.10.053 · Cited by 43 · see citing works
Self-citationDoped semiconductor nanocrystal based fluorescent cellular imaging probes
Maity, A. R., Palmal, S., Basiruddin, S., et al. (2013) · Nanoscale · doi:10.1039/c3nr00549f · Cited by 43 · see citing works
Self-citationQuantitative analysis of COOH-terminated alkanethiol SAMs on gold nanoparticle surfaces
Nguyen, K. C. (2012) · Advances in Natural Sciences Nanoscience and Nanotechnology · doi:10.1088/2043-6262/3/4/045008 · Cited by 39 · see citing works
FRETcalc plugin for calculation of FRET in non-continuous intracellular compartments
Stepensky, D. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.05.180 · Cited by 36 · see citing works
Self-citationCardarelli, F., Serresi, M., Albanese, A., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.203083 · Cited by 29 · see citing works
Kaplun, V., & Stepensky, D. (2014) · Molecular Pharmaceutics · doi:10.1021/mp500253r · Cited by 13 · see citing works
Self-citationSneh-Edri, H., & Stepensky, D. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.01.015 · Cited by 12 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities
Li, L., Hu, S., & Chen, X. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.04.031 · Cited by 415 · see citing works
- Authors
- Maity, A. R., & Stepensky, D.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Corresponding author
- Stepensky, David
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-01-14
- Volume
- 8
- Issue
- 3
- Pages
- 2001-2009
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2230888896
- Cited by
- 44
- References
- 34
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 4
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council for Higher Education
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Quantum Dots Synthesis And Properties
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- quantum dots, nuclear localization signal, nuclear targeting, CdSe/ZnS core-shell nanoparticles, endocytosis, subcellular drug delivery, surface functionalization, peptide adsorption, nanoparticle size and zeta potential
- MeSH terms
- Amino Acid Sequence, Cell Nucleus, Endocytosis, HeLa Cells, Humans, Molecular Sequence Data, Peptides, Endosomes, Subcellular Fractions, Drug Delivery Systems, Nuclear Localization Signals, Quantum Dots, Click Chemistry
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
