Theranostic Layer-by-Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing

Natalie Boehnke; Santiago Correa; Liangliang Hao; Wade Wang; Joelle P Straehla; Sangeeta N Bhatia; Paula T Hammond

doi:10.1002/anie.201911762

Theranostic Layer-by-Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing

Angew Chem Int Ed Engl. 2020 Feb 10;59(7):2776-2783. doi: 10.1002/anie.201911762. Epub 2020 Jan 7.

Authors

Natalie Boehnke¹, Santiago Correa^{1

2

3}, Liangliang Hao^{1

4}, Wade Wang⁵, Joelle P Straehla^{1

6}, Sangeeta N Bhatia^{1

4

7

8

9}, Paula T Hammond^{1

10}

Affiliations

¹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
² Department of Bioengineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
³ Current address: Materials Science and Engineering, Stanford University, 496 Lomita Mall, Stanford, CA, 94305, USA.
⁴ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁵ Department of Chemistry, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁶ Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02115, USA.
⁷ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
⁸ Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02139, USA.
⁹ Howard Hughes Medical Institute, Cambridge, MA, 02139, USA.
¹⁰ Department of Chemical Engineering, 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: gene delivery; layer-by-layer assembly; nanoparticles; self-assembly; theranostics.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Biosensing Techniques
Colorectal Neoplasms / diagnosis*
Colorectal Neoplasms / genetics
Drug Delivery Systems
Female
Gene Silencing
Mice
Nanoparticles / chemistry*
Ovarian Neoplasms / diagnosis*
Ovarian Neoplasms / genetics
Peptides / chemical synthesis
Peptides / chemistry*
Theranostic Nanomedicine*

Substances

Peptides

Abstract

Publication types

MeSH terms

Substances

Grants and funding