Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 7, Pages 1877-1882Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1525796113
Keywords
ligand receptor; mathematical modeling; nanoparticle; phage display; photothermal therapy
Categories
Funding
- Japan Society for the Promotion of Science fellowships
- National Science Foundation [DMS-1562068]
- National Institutes of Health (NIH) [1U54CA149196, 1U54CA143907]
- Lymphoma Leukemia Society [7010-14 SCOR]
- NIH [U01 CA151792-01, R01U54CA143837, 1U54CA151668, P50 CA140388]
- Oncothyreon
- Gillson-Longenbaugh Foundation
- Prostate Cancer Foundation
- Grants-in-Aid for Scientific Research [22112001, 15H05774, 22112002] Funding Source: KAKEN
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A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we showa broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.
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