Full Text | PDF

Theranostics 2022; 12(18):7646-7667. doi:10.7150/thno.78454 This issue Cite

Research Paper

Janus USPION modular platform (JUMP) for theranostic ultrasound-mediated targeted intratumoral microvascular imaging and DNA/miRNA delivery

Ragnhild D. Whitaker^1*, Julius L. Decano^2,3, Catherine Gormley¹, Carl A. Beigie¹, Cari Meisel¹, Glaiza A. Tan^2,3, Ann-Marie Moran^2,3, Nicholas J. Giordano^2,3, Yoonjee Park¹, Peng Huang⁴, Sean Andersson^4,5, Donald Gantz⁶, Aaron K. Grant⁷, Nelson Ruiz-Opazo^2,3, Victoria L.M. Herrera^2,3✉, Joyce Y. Wong^1,2,8✉

1. Department of Biomedical Engineering, Boston University, Boston, MA, USA.
2. Whitaker Cardiovascular Institute, Boston University, Boston, MA, USA.
3. Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
4. Department of Mechanical Engineering, Boston University, Boston, MA, USA.
5. Division of Systems Engineering, Boston University, Boston, MA, USA.
6. Department of Physiology and Biophysics, Boston University, Boston, MA, USA.
7. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
8. Division of Materials Science and Engineering, Boston University, Boston, MA, USA.
* Current address: Aker BioMarine ASA, Lysaker, Norway.

✉ Corresponding authors: Victoria L.M. Herrera (vherreraedu); Joyce Y. Wong (jywongedu)

Abstract

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.

Keywords: Nanomedicine, Janus nanoparticle, pancreatic cancer, nucleic acid delivery, USPION, nano-micro hybrid platform, modular nanotheranostics

Citation styles

©2024 Ivyspring International Publisher. Terms of use