Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release
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. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.
- Authors:
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- Univ. of Tokyo (Japan). Dept. of Molecular Pathology; Univ. of Tokyo Hospital, Tokyo (Japan)
- Univ. of New Mexico, Albuquerque, NM (United States). Comprehensive Cancer Center; Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine
- Univ. of Texas, Houston, TX (United States). M.D. Anderson Cancer Center
- Univ. of Texas Health Science Center at Houston, Houston, TX (United States). Brown Foundation Inst. of Molecular Medicine; Univ. of Texas, Houston, TX (United States). M.D. Anderson Cancer Center
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division
- Oncothyreon, Seattle, WA (United States)
- Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials; Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
- Univ. of Tokyo (Japan). Dept. of Molecular Pathology
- Wayne State Univ., Detroit, MI (United States). Dept. of Biomedical Engineering
- Univ. of Tokyo (Japan). Dept. of Molecular Pathology; Univ. of Tokyo (Japan). Graduate School of Engineering, Dept. of Bioengineering
- Univ. of New Mexico, Albuquerque, NM (United States). Comprehensive Cancer Center; Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials; Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Chemical and Nuclear Engineering
- Harvard Medical School and Dept. of Neurology, Boston, MA (United States). Beth Israel Deaconess Medical Center
- Univ. of New Mexico, Albuquerque, NM (United States). Comprehensive Cancer Center; Univ. of New Mexico School of Medicine, Albuquerque, NM (United States). Division of Hematology/Oncology
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
- Sponsoring Org.:
- USDOE; Japan Society for the Promotion of Science (JSPS); National Science Foundation (NSF); National Institutes of Health (NIH)
- OSTI Identifier:
- 1263534
- Grant/Contract Number:
- DMS-1562068; 1U54CA149196; 1U54CA143907; 7010-14 SCOR; NIH U01 CA151792- 01; R01U54CA143837; 1U54CA151668; P50 CA140388
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 113; Journal Issue: 7; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; photothermal therapy; phage display; nanoparticle; mathematical modeling; ligand receptor
Citation Formats
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, and Pasqualini, Renata. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release. United States: N. p., 2016.
Web. doi:10.1073/pnas.1525796113.
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. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release. United States. https://doi.org/10.1073/pnas.1525796113
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, and Pasqualini, Renata. Tue .
"Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release". United States. https://doi.org/10.1073/pnas.1525796113. https://www.osti.gov/servlets/purl/1263534.
@article{osti_1263534,
title = {Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release},
author = {Hosoya, Hitomi and Dobroff, Andrey S. and Driessen, Wouter H. P. and Cristini, Vittorio and Brinker, Lina M. and Staquicini, Fernanda I. and Cardó-Vila, Marina and D’Angelo, Sara and Ferrara, Fortunato and Proneth, Bettina and Lin, Yu-Shen and Dunphy, Darren R. and Dogra, Prashant and Melancon, Marites P. and Stafford, R. Jason and Miyazono, Kohei and Gelovani, Juri G. and Kataoka, Kazunori and Brinker, C. Jeffrey and Sidman, Richard L. and Arap, Wadih and Pasqualini, Renata},
abstractNote = {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. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.},
doi = {10.1073/pnas.1525796113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 7,
volume = 113,
place = {United States},
year = {Tue Feb 02 00:00:00 EST 2016},
month = {Tue Feb 02 00:00:00 EST 2016}
}
Web of Science
Works referenced in this record:
Odyssey of a cancer nanoparticle: From injection site to site of action
journal, December 2012
- Nichols, Joseph W.; Bae, You Han
- Nano Today, Vol. 7, Issue 6
Nanocarriers for cancer-targeted drug delivery
journal, June 2015
- Kumari, Preeti; Ghosh, Balaram; Biswas, Swati
- Journal of Drug Targeting, Vol. 24, Issue 3
Porous Nanoparticle Supported Lipid Bilayers (Protocells) as Delivery Vehicles
journal, February 2009
- Liu, Juewen; Stace-Naughton, Alison; Jiang, Xingmao
- Journal of the American Chemical Society, Vol. 131, Issue 4, p. 1354-1355
Nanotechnology in cancer therapy
journal, September 2013
- Aslan, Burcu; Ozpolat, Bulent; Sood, Anil K.
- Journal of Drug Targeting, Vol. 21, Issue 10
Gold nanoparticle surface functionalization: a necessary requirement in the development of novel nanotherapeutics
journal, April 2015
- Nicol, James R.; Dixon, Dorian; Coulter, Jonathan A.
- Nanomedicine, Vol. 10, Issue 8
Carbohydrate-Based Nanocarriers Exhibiting Specific Cell Targeting with Minimum Influence from the Protein Corona
journal, May 2015
- Kang, Biao; Okwieka, Patricia; Schöttler, Susanne
- Angewandte Chemie International Edition, Vol. 54, Issue 25
Natural liposomes and synthetic polymeric structures for biomedical applications
journal, December 2015
- Müller, Laura K.; Landfester, Katharina
- Biochemical and Biophysical Research Communications, Vol. 468, Issue 3
Multifunctional Nanoparticles: Cost Versus Benefit of Adding Targeting and Imaging Capabilities
journal, November 2012
- Cheng, Z.; Al Zaki, A.; Hui, J. Z.
- Science, Vol. 338, Issue 6109
Effect of ligand density, receptor density, and nanoparticle size on cell targeting
journal, February 2013
- Elias, Drew R.; Poloukhtine, Andrei; Popik, Vladimir
- Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 9, Issue 2
Ligand-targeted therapeutics in anticancer therapy
journal, October 2002
- Allen, Theresa M.
- Nature Reviews Cancer, Vol. 2, Issue 10
Evaluation of Multivalent, Functional Polymeric Nanoparticles for Imaging Applications
journal, January 2011
- Shokeen, Monica; Pressly, Eric D.; Hagooly, Aviv
- ACS Nano, Vol. 5, Issue 2
MS2 Viruslike Particles: A Robust, Semisynthetic Targeted Drug Delivery Platform
journal, November 2012
- Galaway, Francis A.; Stockley, Peter G.
- Molecular Pharmaceutics, Vol. 10, Issue 1
Virus-modified exosomes for targeted RNA delivery; A new approach in nanomedicine
journal, March 2013
- Koppers-Lalic, Danijela; Hogenboom, Marye M.; Middeldorp, Jaap M.
- Advanced Drug Delivery Reviews, Vol. 65, Issue 3
Reengineering viruses and virus-like particles through chemical functionalization strategies
journal, August 2013
- Smith, Mark Thomas; Hawes, Anna K.; Bundy, Bradley Charles
- Current Opinion in Biotechnology, Vol. 24, Issue 4
On the Synergistic Effects of Ligand-Mediated and Phage-Intrinsic Properties During In Vivo Selection
book, January 2010
- Driessen, Wouter H. P.; Bronk, Lawrence F.; Edwards, Julianna K.
- Tissue-Specific Vascular Endothelial Signals and Vector Targeting, Part B
Bottom-Up Assembly of Hydrogels from Bacteriophage and Au Nanoparticles: The Effect of Cis- and Trans-Acting Factors
journal, May 2008
- Souza, Glauco R.; Yonel-Gumruk, Esra; Fan, Davin
- PLoS ONE, Vol. 3, Issue 5
Networks of gold nanoparticles and bacteriophage as biological sensors and cell-targeting agents
journal, January 2006
- Souza, G. R.; Christianson, D. R.; Staquicini, F. I.
- Proceedings of the National Academy of Sciences, Vol. 103, Issue 5
In Vivo Detection of Gold−Imidazole Self-Assembly Complexes: NIR-SERS Signal Reporters
journal, September 2006
- Souza, Glauco R.; Levin, Carly S.; Hajitou, Amin
- Analytical Chemistry, Vol. 78, Issue 17
Temperature-triggered tumor-specific delivery of anticancer agents by cRGD-conjugated thermosensitive liposomes
journal, April 2014
- Kim, Min Sang; Lee, Don-Wook; Park, Kitae
- Colloids and Surfaces B: Biointerfaces, Vol. 116
Mesoporous Silica Nanoparticle Nanocarriers: Biofunctionality and Biocompatibility
journal, July 2012
- Tarn, Derrick; Ashley, Carlee E.; Xue, Min
- Accounts of Chemical Research, Vol. 46, Issue 3
Molecular Self-Assembly of Aliphatic Thiols on Gold Colloids
journal, January 1996
- Weisbecker, Carl S.; Merritt, Margaret V.; Whitesides, George M.
- Langmuir, Vol. 12, Issue 16
Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity
journal, August 2015
- Maeda, Hiroshi
- Advanced Drug Delivery Reviews, Vol. 91
An unrecognized extracellular function for an intracellular adapter protein released from the cytoplasm into the tumor microenvironment
journal, January 2009
- Mintz, P. J.; Cardo-Vila, M.; Ozawa, M. G.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 7
Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance
journal, November 2003
- Hirsch, L. R.; Stafford, R. J.; Bankson, J. A.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 23, p. 13549-13554
Mechanistic Modeling Identifies Drug-Uptake History as Predictor of Tumor Drug Resistance and Nano-Carrier-Mediated Response
journal, November 2013
- Pascal, Jennifer; Ashley, Carlee E.; Wang, Zhihui
- ACS Nano, Vol. 7, Issue 12
Mechanistic patient-specific predictive correlation of tumor drug response with microenvironment and perfusion measurements
journal, August 2013
- Pascal, J.; Bearer, E. L.; Wang, Z.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 35
Predicting drug pharmacokinetics and effect in vascularized tumors using computer simulation
journal, September 2008
- Sinek, John P.; Sanga, Sandeep; Zheng, Xiaoming
- Journal of Mathematical Biology, Vol. 58, Issue 4-5
Delivery of Small Interfering RNA by Peptide-Targeted Mesoporous Silica Nanoparticle-Supported Lipid Bilayers
journal, February 2012
- Ashley, Carlee E.; Carnes, Eric C.; Epler, Katharine E.
- ACS Nano, Vol. 6, Issue 3
Delivery of Ricin Toxin A-Chain by Peptide-Targeted Mesoporous Silica Nanoparticle-Supported Lipid Bilayers
journal, April 2012
- Epler, Katharine; Padilla, David; Phillips, Genevieve
- Advanced Healthcare Materials, Vol. 1, Issue 3, p. 348-353
The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers
journal, April 2011
- Ashley, Carlee E.; Carnes, Eric C.; Phillips, Genevieve K.
- Nature Materials, Vol. 10, Issue 5, p. 389-397
Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors
journal, March 2015
- Mandelin, Jami; Cardó-Vila, Marina; Driessen, Wouter H. P.
- Proceedings of the National Academy of Sciences
Works referencing / citing this record:
Dendritic Mesoporous Silica Nanoparticles for pH-Stimuli-Responsive Drug Delivery of TNF-Alpha
journal, May 2017
- Kienzle, Arne; Kurch, Sven; Schlöder, Janine
- Advanced Healthcare Materials, Vol. 6, Issue 13
Size‐Optimized Ultrasmall Porous Silica Nanoparticles Depict Vasculature‐Based Differential Targeting in Triple Negative Breast Cancer
journal, September 2019
- Goel, Shreya; Ferreira, Carolina A.; Dogra, Prashant
- Small, Vol. 15, Issue 46
National Cancer Institute Alliance for nanotechnology in cancer—Catalyzing research and translation toward novel cancer diagnostics and therapeutics
journal, June 2019
- Hartshorn, Christopher M.; Russell, Luisa M.; Grodzinski, Piotr
- Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, Vol. 11, Issue 6
Mathematical modeling in cancer nanomedicine: a review
journal, April 2019
- Dogra, Prashant; Butner, Joseph D.; Chuang, Yao-li
- Biomedical Microdevices, Vol. 21, Issue 2
In Vitro Assessment of Fluorine Nanoemulsion-Labeled Hyaluronan-Based Hydrogels for Precise Intrathecal Transplantation of Glial-Restricted Precursors
journal, March 2019
- Piejko, Marcin; Walczak, Piotr; Li, Xiaowei
- Molecular Imaging and Biology, Vol. 21, Issue 6
Imaging of anticancer drug action in single cells
journal, June 2017
- Miller, Miles A.; Weissleder, Ralph
- Nature Reviews Cancer, Vol. 17, Issue 7
Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics
journal, October 2018
- Dogra, Prashant; Adolphi, Natalie L.; Wang, Zhihui
- Nature Communications, Vol. 9, Issue 1
How can nanotechnology help the fight against breast cancer?
journal, January 2018
- Avitabile, Elisabetta; Bedognetti, Davide; Ciofani, Gianni
- Nanoscale, Vol. 10, Issue 25
Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes
journal, October 2016
- Dobroff, Andrey S.; D’Angelo, Sara; Eckhardt, Bedrich L.
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 45
Review of the progress toward achieving heat confinement—the holy grail of photothermal therapy
journal, August 2017
- Sheng, Wangzhong; He, Sha; Seare, William J.
- Journal of Biomedical Optics, Vol. 22, Issue 8
Biomolecular engineering for nanobio/bionanotechnology
journal, April 2017
- Nagamune, Teruyuki
- Nano Convergence, Vol. 4, Issue 1
Bacteriophage-based tools: recent advances and novel applications
journal, January 2016
- O'Sullivan, Lisa; Buttimer, Colin; McAuliffe, Olivia
- F1000Research, Vol. 5
Phage Display Technology and its Applications in Cancer Immunotherapy
journal, May 2019
- Wang, Yicun; Gao, Shuohui; Lv, Jiayin
- Anti-Cancer Agents in Medicinal Chemistry, Vol. 19, Issue 2
Nanoparticles as Theranostic Vehicles in Experimental and Clinical Applications—Focus on Prostate and Breast Cancer
journal, May 2017
- Elgqvist, Jörgen
- International Journal of Molecular Sciences, Vol. 18, Issue 5
Mathematical modeling in cancer nanomedicine: a review
journal, April 2019
- Dogra, Prashant; Butner, Joseph D.; Chuang, Yao-li
- Biomedical Microdevices, Vol. 21, Issue 2
Nanotechnology-based strategies for treatment of ocular disease
journal, May 2017
- Weng, Yuhua; Liu, Juan; Jin, Shubin
- Acta Pharmaceutica Sinica B, Vol. 7, Issue 3
An AAVP-based solid-phase transducing matrix for transgene delivery: potential for translational applications
journal, May 2017
- Smith, T. L.; Souza, G. R.; Sidman, R. L.
- Cancer Gene Therapy, Vol. 24, Issue 8
Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics
journal, October 2018
- Dogra, Prashant; Adolphi, Natalie L.; Wang, Zhihui
- Nature Communications, Vol. 9, Issue 1
Biomolecular engineering for nanobio/bionanotechnology
journal, April 2017
- Nagamune, Teruyuki
- Nano Convergence, Vol. 4, Issue 1
Nanoparticles as Theranostic Vehicles in Experimental and Clinical Applications—Focus on Prostate and Breast Cancer
journal, May 2017
- Elgqvist, Jörgen
- International Journal of Molecular Sciences, Vol. 18, Issue 5