Journal
THERANOSTICS
Volume 12, Issue 18, Pages 7646-7667Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.78454
Keywords
Nanomedicine; Janus nanoparticle; pancreatic cancer; nucleic acid delivery; USPION; nano-micro hybrid platform; modular nanotheranostics
Categories
Funding
- BUSM Department of Medicine
- BU Nanotechnology Innovation Center
- Nano theranostics Affinity Research Collaborative (ARC)
- Evans Center for Interdisciplinary Biomedical Research
- Ultra-sound Micro-Imaging Core
- Department of Biomedical Engineering Bio interface CORE facility
- BU-Clinical and Translational Science Institute grant [NIH-U54TR001012]
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This study reports a Janus-nanoparticle (jNP) system with multifunctional targeting, payload delivery, and targeted imaging capabilities, which shows potential breakthroughs in cancer therapy and diagnostics.
Rationale: High mortality in pancreatic cancer (PDAC) and triple negative breast cancer (TNBC) highlight the need to capitalize on nanoscale-design advantages for multifunctional diagnostics and therapies. DNA/RNA-therapies can provide potential breakthroughs, however, to date, there is no FDA-approved systemic delivery system to solid tumors.Methods: Here, we report a Janus-nanoparticle (jNP)-system with modular targeting, payload-delivery, and targeted-imaging capabilities. Our jNP-system consists of 10 nm ultrasmall superparamagnetic iron oxide nanoparticles (USPION) with opposing antibody-targeting and DNA/RNA payload-protecting faces, directionally self-assembled with commercially available zwitterionic microbubbles (MBs) and DNA/RNA payloads.Results: Sonoporation of targeted jNP-payload-MBs delivers functional reporter-DNA imparting tumor-fluorescence, and micro-RNA126 reducing non-druggable KRAS in PDAC-Panc1 and TNBC-MB231 xenografted tumors. The targeting jNP-system enhances ultrasound-imaging of intra-tumoral microvasculature using less MBs/body weight (BW). The jNP-design enhances USPION's T2*-magnetic resonance (MR) and MR-imaging of PDAC-peritoneal metastases using less Fe/BW.Conclusion: Altogether, data advance the asymmetric jNP-design as a potential theranostic Janus-USPION Modular Platform - a JUMP forward.
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