Antitumor Activity of Death Receptor 5-Targeted Camptothecin-Loaded Nanoparticles in Murine Syngeneic Models

Anna J Boland1, Michelle K Greene1,2, Úna M Herron1,2

  • 1The Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7AE, United Kingdom.

Biomacromolecules
|December 10, 2025
PubMed

Insights

Targeting cancer cells with nanoparticles that activate death receptor 5 (DR5) effectively inhibits tumor growth in immunocompetent mice. This approach shows promise for cancer therapy by leveraging the extrinsic apoptotic pathway.

Area of Science:

  • Oncology
  • Nanomedicine
  • Immunology

Background:

  • Death receptor 5 (DR5) is crucial for extrinsic apoptosis and is upregulated in tumors, making it a therapeutic target.
  • Nanoparticle-based DR5 agonists can induce tumor cell death, but efficacy in immunocompetent models is not well-established.

Purpose of the Study:

  • To develop and evaluate camptothecin-loaded polymeric nanoparticles coated with a murine DR5 antibody (MD5-1) for cancer therapy.
  • To assess the *in vitro* and *in vivo* antitumor efficacy of these DR5-targeted nanoparticles in syngeneic murine models.

Main Methods:

  • Polymeric nanoparticles loaded with camptothecin and coated with the MD5-1 antibody were synthesized.
  • Pro-apoptotic effects were evaluated *in vitro* in murine cell lines.
  • Antitumor efficacy was assessed *in vivo* using MC38 colorectal allografts in mice, comparing targeted nanoparticles to controls.

Main Results:

  • The DR5-targeted nanoparticles demonstrated significant pro-apoptotic effects *in vitro*.
  • These nanoparticles inhibited MC38 colorectal allograft growth by over 90% compared to control nanoparticles *in vivo*.

Conclusions:

  • DR5-targeted nanoparticles exhibit potent antitumor activity in syngeneic models, confirming their therapeutic potential.
  • This study validates the use of DR5-targeted nanoparticles in immunocompetent hosts and suggests further investigation into their effects on tumor immunity.