Engineered Ultrasmall Nanoparticle Drug-Immune Conjugates with "Hit and Run" Tumor Delivery to Eradicate Gastric Cancer.

Autor: Zhang L; Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA., Aragon-Sanabria V; Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA., Aditya A; Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA., Marelli M; AstraZeneca, One MedImmune Way, Gaithersburg, MD 20878, United States., Cao T; Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA., Chen F; Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA., Yoo B; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; Department of Chemistry, Hunter College, New York, NY 10065, USA., Ma K; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; Department of Materials Science & Engineering, Cornell University, Ithaca, NY 14853, USA., Zhuang L; AstraZeneca, One MedImmune Way, Gaithersburg, MD 20878, United States., Cailleau T; AstraZeneca, Spirogen, QMB Innovation Centre, 42 New Road, London E1 2AX, UK., Masterson L; AstraZeneca, Spirogen, QMB Innovation Centre, 42 New Road, London E1 2AX, UK., Turker MZ; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; Department of Materials Science & Engineering, Cornell University, Ithaca, NY 14853, USA., Lee R; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; Department of Materials Science & Engineering, Cornell University, Ithaca, NY 14853, USA., DeLeon G; Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA., Monette S; Laboratory of Comparative Pathology, Sloan Kettering Institute for Cancer Research, Weill Cornell Medicine, The Rockefeller University, New York, NY 10065, USA., Colombo R; AstraZeneca, One MedImmune Way, Gaithersburg, MD 20878, United States., Christie RJ; AstraZeneca, One MedImmune Way, Gaithersburg, MD 20878, United States., Zanzonico P; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; Department of Medical Physics, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA., Wiesner U; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; Department of Materials Science & Engineering, Cornell University, Ithaca, NY 14853, USA.; Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, NY 14853, USA., Subramony JA; AstraZeneca, One MedImmune Way, Gaithersburg, MD 20878, United States., Bradbury MS; Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; MSK-Cornell Center for Translation of Cancer Nanomedicines, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.; Molecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
Jazyk: angličtina
Zdroj: Advanced therapeutics [Adv Ther (Weinh)] 2023 Mar; Vol. 6 (3). Date of Electronic Publication: 2022 Oct 19.
DOI: 10.1002/adtp.202370009
Abstrakt: Despite advances by recently approved antibody-drug conjugates in treating advanced gastric cancer patients, substantial limitations remain. Here, several key obstacles are overcome by developing a first-in-class ultrasmall (sub-8-nanometer (nm)) anti-human epidermal growth factor receptor 2 (HER2)-targeting drug-immune conjugate nanoparticle therapy. This multivalent fluorescent core-shell silica nanoparticle bears multiple anti-HER2 single-chain variable fragments (scFv), topoisomerase inhibitors, and deferoxamine moieties. Most surprisingly, drawing upon its favorable physicochemical, pharmacokinetic, clearance, and target-specific dual-modality imaging properties in a "hit and run" approach, this conjugate eradicated HER2-expressing gastric tumors without any evidence of tumor regrowth, while exhibiting a wide therapeutic index. Therapeutic response mechanisms are accompanied by the activation of functional markers, as well as pathway-specific inhibition. Results highlight the potential clinical utility of this molecularly engineered particle drug-immune conjugate and underscore the versatility of the base platform as a carrier for conjugating an array of other immune products and payloads.
Competing Interests: Conflict of Interest M.S.B., U.W., F.C., K.M., and M.Z.T. hold interest in, and U.W. a board seat of, Elucida Oncology, Inc., which has licensed IP from Cornell and MSK on C′ dots and their application in oncology. The remaining authors declare no conflict of interest.
Databáze: MEDLINE
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