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Smart exosomes enhance PDAC targeted therapy.
Creeden, Justin F; Sevier, Jonathan; Zhang, Jian-Ting; Lapitsky, Yakov; Brunicardi, F Charles; Jin, Ge; Nemunaitis, John; Liu, Jing-Yuan; Kalinoski, Andrea; Rao, Donald; Liu, Shi-He.
Afiliación
  • Creeden JF; Department of Cell and Cancer Biology, University of Toledo, Toledo, OH, USA.
  • Sevier J; Department of Cell and Cancer Biology, University of Toledo, Toledo, OH, USA.
  • Zhang JT; Department of Cell and Cancer Biology, University of Toledo, Toledo, OH, USA.
  • Lapitsky Y; Department of Chemical Engineering, University of Toledo, Toledo, OH, USA.
  • Brunicardi FC; Department of Surgery, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
  • Jin G; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Nemunaitis J; Gradalis Inc., Dallas, TX, USA.
  • Liu JY; Department of Medicine, University of Toledo, Toledo, OH, USA.
  • Kalinoski A; Department of Surgery, University of Toledo, Toledo, OH, USA.
  • Rao D; Gradalis Inc., Dallas, TX, USA.
  • Liu SH; Department of Cell and Cancer Biology, University of Toledo, Toledo, OH, USA. Electronic address: shi-he.liu@utoledo.edu.
J Control Release ; 368: 413-429, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38431093
ABSTRACT
Exosomes continue to attract interest as a promising nanocarrier drug delivery technology. They are naturally derived nanoscale extracellular vesicles with innate properties well suited to shuttle proteins, lipids, and nucleic acids between cells. Nonetheless, their clinical utility is currently limited by several major challenges, such as their inability to target tumor cells and a high proportion of clearance by the mononuclear phagocyte system (MPS) of the liver and spleen. To overcome these limitations, we developed "Smart Exosomes" that co-display RGD and CD47p110-130 through CD9 engineering (ExoSmart). The resultant ExoSmart demonstrates enhanced binding capacity to αvß3 on pancreatic ductal adenocarcinoma (PDAC) cells, resulting in amplified cellular uptake in in vitro and in vivo models and increased chemotherapeutic efficacies. Simultaneously, ExoSmart significantly reduced liver and spleen clearance of exosomes by inhibiting macrophage phagocytosis via CD47p110-130 interaction with signal regulatory proteins (SIRPα) on macrophages. These studies demonstrate that an engineered exosome drug delivery system increases PDAC therapeutic efficacy by enhancing active PDAC targeting and prolonging circulation times, and their findings hold tremendous translational potential for cancer therapy while providing a concrete foundation for future work utilizing novel peptide-engineered exosome strategies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Exosomas Límite: Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Exosomas Límite: Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos