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Theranostic Layer-by-Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing
Natalie Boehnke1, Santiago Correa1,2,3, Liangliang Hao1,4
1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Angewandte Chemie (International Ed. in English)
|November 21, 2019
Summary
We developed novel nanotheranostics for cancer diagnosis and treatment. These nanoparticles detect tumor proteases in urine and deliver gene silencing therapy, aiding in early cancer detection and prognosis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Molecular Biology
Background:
- Layer-by-layer nanoparticles (NPs) are versatile drug delivery systems.
- NPs can be functionalized for targeted delivery and diagnostics.
Purpose of the Study:
- To create a novel nanotheranostic combining layer-by-layer assembly with biosensing peptides.
- To develop a system for noninvasive cancer diagnostics and gene silencing therapy.
Main Methods:
- Synthesized layer-by-layer nanoparticles encapsulating siRNA.
- Functionalized NPs with a synthetic biosensing peptide cleaved by tumor-specific proteases (MMP9).
- Evaluated diagnostic capabilities via urinary reporter detection and therapeutic efficacy through gene silencing in mouse cancer models.
Main Results:
- Nanotheranostics successfully detected MMP9 overexpression in mouse models of three cancer types.
- Demonstrated simultaneous gene silencing in flank and metastatic ovarian cancer models.
- Achieved noninvasive, urinary-based diagnostics linked to metastatic tumors and poor prognosis.
Conclusions:
- This nanotheranostic platform enables early detection of metastatic cancer through urinary biomarkers.
- The system offers simultaneous gene silencing therapy, improving treatment potential.
- Represents a significant advancement in theranostics for oncology.
