Author:
Hosoya Hitomi,Dobroff Andrey S.,Driessen Wouter H. P.,Cristini Vittorio,Brinker Lina M.,Staquicini Fernanda I.,Cardó-Vila Marina,D’Angelo Sara,Ferrara Fortunato,Proneth Bettina,Lin Yu-Shen,Dunphy Darren R.,Dogra Prashant,Melancon Marites P.,Stafford R. Jason,Miyazono Kohei,Gelovani Juri G.,Kataoka Kazunori,Brinker C. Jeffrey,Sidman Richard L.,Arap Wadih,Pasqualini Renata
Abstract
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 show a 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.
Funder
Japan Society for the Promotion of Science
National Science Foundation
NIH
KAU
Lumphoma Leukemia Society
Oncothyreon
Gillson-Longenbaugh Foundation and the Prostate Cancer Foundation
Publisher
Proceedings of the National Academy of Sciences
Cited by
55 articles.
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