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DNA complex-releasing system by injectable self-setting apatite cement.

Tomoko Ito1, Yoshiyuki Koyama, Makoto Otsuka

  • 1Musashino University, Research Institute of Pharmaceutical Sciences, Tokyo, Japan.

The Journal of Gene Medicine
|February 28, 2012
PubMed
Summary

Injectable apatite cement loaded with plasmid DNA (pDNA)-GM-CSF complexes offers sustained gene expression for effective solid tumor treatment. This novel system demonstrates significant therapeutic potential with a single injection, leading to complete tumor disappearance in many cases.

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Area of Science:

  • Biomedical Engineering
  • Gene Therapy
  • Materials Science

Background:

  • Plasmid DNA complexes have limited therapeutic efficacy due to short gene expression duration.
  • Instability of DNA/polycation complexes hinders efficient DNA slow-release systems.
  • Hyaluronan (HA) stabilizes DNA/polycation complexes, enabling the creation of very small particles.

Purpose of the Study:

  • To develop a durable gene expression system using injectable self-setting apatite cement.
  • To incorporate DNA/polycation/HA complexes into apatite cement for sustained release.
  • To evaluate the therapeutic effect of this novel gene delivery system on solid tumors.

Main Methods:

  • DNA/polyethyleneimine (PEI)/HA complex particles were prepared via lyophilization and rehydration.

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  • In vitro DNA complex release from apatite cement was assessed using MLC-6 cells.
  • Apatite cement containing pDNA-GM-CSF complexes was injected subcutaneously into tumor-bearing mice.
  • Main Results:

    • DNA/PEI/HA complexes remained dispersed within the apatite cement.
    • Continuous release of DNA complexes from the apatite cement was observed.
    • A single injection led to complete tumor disappearance in 60% of mice, with smooth cement degradation.

    Conclusions:

    • Injectable apatite cement containing pDNA-GM-CSF complexes demonstrates significant therapeutic effects on solid tumors.
    • This system shows promise as a sustained gene expression device for cancer therapy.
    • The combination of apatite cement and DNA complexes offers a viable strategy for durable gene delivery.