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

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jan 07, 2020
Source ID
10.1002/ange.201911762

Entities

People

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

Organizations

  • Dana–Farber Cancer Institute
  • Harvard Medical School
  • Howard Hughes Medical Institute
  • Massachusetts Institute of Technology
  • National Cancer Institute
  • National Institutes of Health
  • Stanford University
  • United States Department of Defense

Tags

Readers

  • Molecular Biology and Genetics
  • Molecular Genetics
  • Nanocomposite Materials Science

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech