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Delivery systems exploiting natural cell transport processes of macromolecules for intracellular targeting of Auger electron emitters.

Publication ,  Journal Article
Rosenkranz, AA; Slastnikova, TA; Georgiev, GP; Zalutsky, MR; Sobolev, AS
Published in: Nucl Med Biol
2020

The presence of Auger electrons (AE) among the decay products of a number of radionuclides makes these radionuclides an attractive means for treating cancer because these short-range electrons can cause significant damage in the immediate vicinity of the decomposition site. Moreover, the extreme locality of the effect provides a potential for selective eradication of cancer cells with minimal damage to adjacent normal cells provided that the delivery of the AE emitter to the most vulnerable parts of the cell can be achieved. Few cellular compartments have been regarded as the desired target site for AE emitters, with the cell nucleus generally recognized as the preferred site for AE decay due to the extreme sensitivity of nuclear DNA to direct damage by radiation of high linear energy transfer. Thus, the advantages of AE emitters for cancer therapy are most likely to be realized by their selective delivery into the nucleus of the malignant cells. To achieve this goal, delivery systems must combine a challenging complex of properties that not only provide cancer cell preferential recognition but also cell entry followed by transport into the cell nucleus. A promising strategy for achieving this is the recruitment of natural cell transport processes of macromolecules, involved in each of the aforementioned steps. To date, a number of constructs exploiting intracellular transport systems have been proposed for AE emitter delivery to the nucleus of a targeted cell. An example of such a multifunctional vehicle that provides smart step-by-step delivery is the so-called modular nanotransporter, which accomplishes selective recognition, binding, internalization, and endosomal escape followed by nuclear import of the delivered radionuclide. The current review will focus on delivery systems utilizing various intracellular transport pathways and their combinations in order to provide efficient targeting of AE to the cancer cell nucleus.

Duke Scholars

Published In

Nucl Med Biol

DOI

EISSN

1872-9614

Publication Date

2020

Volume

80-81

Start / End Page

45 / 56

Location

United States

Related Subject Headings

  • Nuclear Medicine & Medical Imaging
  • Molecular Targeted Therapy
  • Intracellular Space
  • Humans
  • Electrons
  • Biological Transport
  • Animals
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rosenkranz, A. A., Slastnikova, T. A., Georgiev, G. P., Zalutsky, M. R., & Sobolev, A. S. (2020). Delivery systems exploiting natural cell transport processes of macromolecules for intracellular targeting of Auger electron emitters. Nucl Med Biol, 8081, 45–56. https://doi.org/10.1016/j.nucmedbio.2019.11.005
Rosenkranz, Andrey A., Tatiana A. Slastnikova, Georgii P. Georgiev, Michael R. Zalutsky, and Alexander S. Sobolev. “Delivery systems exploiting natural cell transport processes of macromolecules for intracellular targeting of Auger electron emitters.Nucl Med Biol 80–81 (2020): 45–56. https://doi.org/10.1016/j.nucmedbio.2019.11.005.
Rosenkranz AA, Slastnikova TA, Georgiev GP, Zalutsky MR, Sobolev AS. Delivery systems exploiting natural cell transport processes of macromolecules for intracellular targeting of Auger electron emitters. Nucl Med Biol. 2020;80–81:45–56.
Rosenkranz, Andrey A., et al. “Delivery systems exploiting natural cell transport processes of macromolecules for intracellular targeting of Auger electron emitters.Nucl Med Biol, vol. 80–81, 2020, pp. 45–56. Pubmed, doi:10.1016/j.nucmedbio.2019.11.005.
Rosenkranz AA, Slastnikova TA, Georgiev GP, Zalutsky MR, Sobolev AS. Delivery systems exploiting natural cell transport processes of macromolecules for intracellular targeting of Auger electron emitters. Nucl Med Biol. 2020;80–81:45–56.
Journal cover image

Published In

Nucl Med Biol

DOI

EISSN

1872-9614

Publication Date

2020

Volume

80-81

Start / End Page

45 / 56

Location

United States

Related Subject Headings

  • Nuclear Medicine & Medical Imaging
  • Molecular Targeted Therapy
  • Intracellular Space
  • Humans
  • Electrons
  • Biological Transport
  • Animals
  • 3202 Clinical sciences
  • 1103 Clinical Sciences