2. Academic Validation
  3. Combination non-targeted and sGRP78-targeted nanoparticle drug delivery outperforms either component to treat metastatic ovarian cancer

Combination non-targeted and sGRP78-targeted nanoparticle drug delivery outperforms either component to treat metastatic ovarian cancer

  • J Control Release. 2024 Nov:375:438-453. doi: 10.1016/j.jconrel.2024.09.014.
Jenna N Sjoerdsma 1,  Emily K Bromley 1,  Jaeho Shin 1,  Tyvette Hilliard 2,  Yueying Liu 2,  Caitlin Horgan 3,  Gyoyeon Hwang 1,  Michael Bektas 2,  David Omstead 4,  Tanyel Kiziltepe 1,  M Sharon Stack 5,  Basar Bilgicer 6
Affiliations

Affiliations

  • 1 Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Berthiaume Institute for Precision Health, University of Notre Dame, Notre Dame, IN 46556, USA.
  • 2 Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
  • 3 Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Berthiaume Institute for Precision Health, University of Notre Dame, Notre Dame, IN 46556, USA; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
  • 4 Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • 5 Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: Sharon.Stack.11@nd.edu.
  • 6 Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Berthiaume Institute for Precision Health, University of Notre Dame, Notre Dame, IN 46556, USA; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA; Center for Rare & Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: BBilgicer@nd.edu.
PMID: 39271060 DOI: 10.1016/j.jconrel.2024.09.014
Abstract

Metastatic ovarian Cancer (MOC) is highly deadly, due in part to the limited efficacy of standard-of-care chemotherapies to metastatic tumors and non-adherent Cancer cells. Here, we demonstrated the effectiveness of a combination therapy of GRP78-targeted (TNPGRP78pep) and non-targeted (NP) nanoparticles to deliver a novel DM1-prodrug to MOC in a syngeneic mouse model. Cell surface-GRP78 is overexpressed in MOC, making GRP78 an optimal target for selective delivery of nanoparticles to MOC. The NP + TNPGRP78pep combination treatment reduced tumor burden by 15-fold, compared to untreated control. Increased T cell and macrophage levels in treated groups also suggested antitumor immune system involvement. The NP and TNPGRP78pep components functioned synergistically through two proposed mechanisms of action. The TNPGRP78pep targeted non-adherent Cancer cells in the peritoneal cavity, preventing the formation of new solid tumors, while the NP passively targeted existing solid tumor sites, providing a sustained release of the drug to the tumor microenvironment.

Keywords

Antitumor immune response; Lipid nanoparticle; Metastasis; Ovarian cancer; Targeted drug delivery; women's health.

Figures
Products