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Theranostic Layer-by-Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing |
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| Authors: | Dr Natalie Boehnke Dr Santiago Correa Dr Liangliang Hao Dr Wade Wang Dr Joelle P Straehla Prof Sangeeta N Bhatia Prof Paula T Hammond |
| Institution: | 1. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA
These authors contributed equally to this work.;2. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA Department of Bioengineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA Current address: Materials Science and Engineering, Stanford University, 496 Lomita Mall, Stanford, CA, 94305 USA These authors contributed equally to this work.;3. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA These authors contributed equally to this work.;4. Department of Chemistry, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA;5. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02115 USA;6. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115 USA Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02139 USA Howard Hughes Medical Institute, Cambridge, MA, 02139 USA;7. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA |
| Abstract: | Layer-by-layer nanoparticles (NPs) are modular drug delivery vehicles that incorporate multiple functional materials through sequential deposition of polyelectrolytes onto charged nanoparticle cores. Herein, we combined the multicomponent features and tumor targeting capabilities of layer-by-layer assembly with functional biosensing peptides to create a new class of nanotheranostics. These NPs encapsulate a high weight percentage of siRNA while also carrying a synthetic biosensing peptide on the surface that is cleaved into a urinary reporter upon exposure to specific proteases overexpressed in the tumor microenvironment. Importantly, this biosensor reports back on a molecular signature characteristic to metastatic tumors and associated with poor prognosis, MMP9 protease overexpression. This nanotheranostic mediates noninvasive urinary-based diagnostics in mouse models of three different cancers with simultaneous gene silencing in flank and metastatic mouse models of ovarian cancer. |
| Keywords: | Gen-Übertragung Nanopartikel Schichtweiser Aufbau Selbstassemblierung Theranostik |