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Combination non-targeted and sGRP78-targeted nanoparticle drug delivery outperforms either component to treat metastatic ovarian cancer.
Sjoerdsma, Jenna N; Bromley, Emily K; Shin, Jaeho; Hilliard, Tyvette; Liu, Yueying; Horgan, Caitlin; Hwang, Gyoyeon; Bektas, Michael; Omstead, David; Kiziltepe, Tanyel; Stack, M Sharon; Bilgicer, Basar.
Affiliation
  • Sjoerdsma JN; 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.
  • Bromley EK; 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.
  • Shin J; 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.
  • Hilliard T; 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.
  • Liu Y; 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.
  • Horgan C; 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.
  • Hwang G; 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.
  • Bektas M; 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.
  • Omstead D; 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.
  • Kiziltepe T; 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.
  • Stack MS; 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.
  • Bilgicer B; 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; Departmen
J Control Release ; 375: 438-453, 2024 Sep 19.
Article in En | MEDLINE | ID: mdl-39271060
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: J Control Release Year: 2024 Document type: Article
Fulltext
Print
XML
PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: J Control Release Year: 2024 Document type: Article