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STING activation disrupts tumor vasculature to overcome the EPR limitation and increase drug deposition.
Jiang, Xiaomin; Luo, Taokun; Yang, Kaiting; Lee, Morten J; Liu, Jing; Tillman, Langston; Zhen, Wenyao; Weichselbaum, Ralph R; Lin, Wenbin.
Afiliación
  • Jiang X; Department of Chemistry, The University of Chicago, 929 E 57th St, Chicago, IL 60637, USA.
  • Luo T; Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago, 5758 S Maryland Ave., Chicago, IL 60637, USA.
  • Yang K; Department of Chemistry, The University of Chicago, 929 E 57th St, Chicago, IL 60637, USA.
  • Lee MJ; Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago, 5758 S Maryland Ave., Chicago, IL 60637, USA.
  • Liu J; Department of Chemistry, The University of Chicago, 929 E 57th St, Chicago, IL 60637, USA.
  • Tillman L; Department of Chemistry, The University of Chicago, 929 E 57th St, Chicago, IL 60637, USA.
  • Zhen W; Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago, 5758 S Maryland Ave., Chicago, IL 60637, USA.
  • Weichselbaum RR; Department of Chemistry, The University of Chicago, 929 E 57th St, Chicago, IL 60637, USA.
  • Lin W; Department of Chemistry, The University of Chicago, 929 E 57th St, Chicago, IL 60637, USA.
Sci Adv ; 10(29): eado0082, 2024 Jul 19.
Article en En | MEDLINE | ID: mdl-39018400
ABSTRACT
The low success rate of cancer nanomedicines has raised debate on the role of the enhanced permeability and retention (EPR) effect on tumor deposition of nanotherapeutics. Here, we report a bifunctional nanoscale coordination polymer (NCP), oxaliplatin (OX)/2',3'-cyclic guanosine monophosphate-adenosine monophosphate (GA), to overcome the EPR limitation through stimulator of interferon genes (STING) activation and enhance chemotherapeutic and STING agonist delivery for tumor eradication. OX/GA encapsulates GA and OX in the NCP to protect GA from enzymatic degradation and improve GA and OX pharmacokinetics. STING activation by OX/GA disrupts tumor vasculatures and increases intratumoral deposition of OX by 4.9-fold over monotherapy OX-NCP. OX/GA demonstrates exceptional antitumor effects with >95% tumor growth inhibition and high cure rates in subcutaneous, orthotopic, spontaneous, and metastatic tumor models. OX/GA induces immunogenic cell death of tumor cells and STING activation of innate immune cells to enhance antigen presentation. NCPs provide an excellent nanoplatform to overcome the EPR limitation for effective cancer therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos