Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

Hitomi Hosoya, Andrey S Dobroff, Wouter H P Driessen, Vittorio Cristini, Lina M Brinker, Fernanda I Staquicini, Marina Cardó-Vila, Sara D'Angelo, Fortunato Ferrara, Bettina Proneth, Yu-Shen Lin, Darren R Dunphy, Prashant Dogra, Marites P Melancon, R Jason Stafford, Kohei Miyazono, Juri G Gelovani, Kazunori Kataoka, C Jeffrey Brinker, Richard L SidmanWadih Arap, Renata Pasqualini

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1877-82
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number7
DOIs
StatePublished - Feb 16 2016

Keywords

  • Animals
  • Antineoplastic Agents
  • Breast Neoplasms
  • Disease Models, Animal
  • Drug Delivery Systems
  • Female
  • Infrared Rays
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Multimodal Imaging
  • Nanotechnology
  • Prostatic Neoplasms
  • Surface Plasmon Resonance
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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