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PSMA targeted conjugates based on dextran.

Magdalena Janczewska1, Michał Szkop2, Grzegorz Pikus3

  • 1NanoThea Inc., Rakowiecka 36, 02-532 Warsaw, Poland; Warsaw University of Technology, Faculty of Chemical and Process Engineering, Waryńskiego 1, 00-645 Warsaw, Poland.

Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine
|October 21, 2020
PubMed
Summary

We developed novel dextran-based radioconjugates for targeted cancer therapy, improving radiochemical properties and selective cell uptake. This new method enhances therapeutic efficacy while minimizing side effects.

Keywords:
DOTA-ConjugatesDextranNanoparticlesProstate cancerRadioconjugates

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Area of Science:

  • Radiopharmaceutical Chemistry
  • Nanotechnology in Medicine
  • Cancer Therapeutics

Background:

  • Radiotherapy is a cornerstone of cancer treatment but can cause significant side effects.
  • Targeted radiopharmaceuticals offer a strategy to enhance therapeutic efficacy and reduce off-target toxicity.
  • Dextran-based carriers are explored for their potential in drug delivery and targeted therapies.

Purpose of the Study:

  • To investigate two synthetic pathways for dextran-based radiocarriers.
  • To evaluate the chemical, physical, and biological properties of these radioconjugates.
  • To assess the influence of conjugate structure on biological interactions and radiolabeling efficiency.

Main Methods:

  • Synthesis and characterization of dextran-based micelle-like nanoparticles (NPs) and non-folded conjugates.
  • Attachment and quantification of PSMA small molecule inhibitor using DELFIA fluorescence assay.
  • Assessment of cellular uptake mechanisms via confocal microscopy and ITLC-SG chromatography.

Main Results:

  • Two distinct dextran-based conjugates (NPs and non-folded) were successfully synthesized.
  • Conjugate tertiary structure influenced PSMA selectivity, cell binding, and uptake mechanisms.
  • TCT-amine bonding demonstrated superior stability (99.8-100% yield) compared to NHS-coupled DOTA (91.3-97.7% yield).

Conclusions:

  • Novel dextran-based radioconjugates were developed with improved radiochemical properties.
  • A superior chelator binding method was identified, enhancing stability and yield.
  • The study demonstrated selective cross-membrane transport mediated by conjugate structure.