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.
Proceedings of the National Academy of Sciences of the United States of America. 2016 Feb 02 [Epub ahead of print]
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 Sidman, Wadih Arap, Renata Pasqualini
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8656, Japan; The University of Tokyo Hospital, Tokyo 113-8656, Japan;, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131;, David H. Koch Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;, Department of NanoMedicine and BioMedical Engineering, School of Medicine, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77054; Department of Proteomics and Systems Biology, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77054; Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77054;, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131;, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131;, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131;, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545;, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545;, David H. Koch Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;, Oncothyreon, Seattle, WA 98121;, Center for Micro-Engineered Materials, University of New Mexico, Albuquerque, NM 87131; Sandia National Laboratories, Albuquerque, NM 87106;, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131;, Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77054;, Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77054;, Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8656, Japan;, Department of Biomedical Engineering, Wayne State University, Detroit, MI 48201;, Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8656, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan;, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; Center for Micro-Engineered Materials, University of New Mexico, Albuquerque, NM 87131; Sandia National Laboratories, Albuquerque, NM 87106; Department of Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, NM 87131;, Harvard Medical School and Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; Division of Hematology/Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131 University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131;