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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...

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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
14:20

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Published on: June 13, 2014

Nanoconjugate based on polymalic acid for tumor targeting.

Julia Y Ljubimova1, Manabu Fujita, Natalya M Khazenzon

  • 1Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, USA. ljubimovaj@cshs.org

Chemico-Biological Interactions
|March 23, 2007
PubMed
Summary

A novel nanoconjugate, Polycefin, demonstrates effective tumor accumulation via enhanced permeability and retention (EPR) effect and receptor-mediated endocytosis. This polymer-derived system targets drug delivery, showing significant accumulation in both breast and brain tumors in vivo.

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Drug Delivery Systems

Background:

  • Targeted drug delivery remains a significant challenge in cancer therapy.
  • Polymer-derived nanoconjugates offer potential for enhanced therapeutic efficacy.
  • The enhanced permeability and retention (EPR) effect and receptor-mediated endocytosis are key mechanisms for tumor targeting.

Purpose of the Study:

  • To evaluate the tumor-targeting capability of a novel nanoconjugate, Polycefin.
  • To assess Polycefin's accumulation in breast and brain tumors using in vivo imaging.
  • To investigate the potential of Polycefin for delivering Morpholino antisense oligonucleotides.

Main Methods:

  • Synthesis of Polycefin, a polymer-derived nanoconjugate using poly(beta-l-malic acid).
  • Coupling Polycefin with AlexaFluor 680 C2-maleimide dye for fluorescence imaging.
  • In vivo fluorescence imaging of tumor-bearing nude mice (MDA-MB 468 breast cancer, U87MG glioma) after intravenous injection of Polycefin.
  • Histological examination of organs to corroborate imaging data.

Main Results:

  • Polycefin demonstrated rapid and significant accumulation in breast tumors, reaching levels 6 times higher than non-tumor tissue within 180 minutes.
  • Selective accumulation of Polycefin was observed in brain tumors within 24 hours, with minimal signal in surrounding non-tumor areas.
  • Fluorescence was primarily detected in tumors, kidneys, and liver, indicating tumor-specific accumulation and clearance pathways.

Conclusions:

  • Polycefin effectively accumulates in tumors through EPR effect and receptor-mediated endocytosis.
  • The nanoconjugate shows promise for targeted delivery of therapeutic agents to both breast and brain tumors.
  • Polycefin is a biodegradable, non-immunogenic, and non-toxic system with potential for clinical translation.