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

Autor:	Whitaker RD; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Decano JL; Whitaker Cardiovascular Institute, Boston University, Boston, MA, USA.; Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Gormley C; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Beigie CA; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Meisel C; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Tan GA; Whitaker Cardiovascular Institute, Boston University, Boston, MA, USA.; Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Moran AM; Whitaker Cardiovascular Institute, Boston University, Boston, MA, USA.; Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Giordano NJ; Whitaker Cardiovascular Institute, Boston University, Boston, MA, USA.; Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Park Y; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Huang P; Department of Mechanical Engineering, Boston University, Boston, MA, USA., Andersson S; Department of Mechanical Engineering, Boston University, Boston, MA, USA.; Division of Systems Engineering, Boston University, Boston, MA, USA., Gantz D; Department of Physiology and Biophysics, Boston University, Boston, MA, USA., Grant AK; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Ruiz-Opazo N; Whitaker Cardiovascular Institute, Boston University, Boston, MA, USA.; Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Herrera VLM; Whitaker Cardiovascular Institute, Boston University, Boston, MA, USA.; Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Wong JY; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; Whitaker Cardiovascular Institute, Boston University, Boston, MA, USA.; Division of Materials Science and Engineering, Boston University, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	Theranostics [Theranostics] 2022 Nov 07; Vol. 12 (18), pp. 7646-7667. Date of Electronic Publication: 2022 Nov 07 (Print Publication: 2022).
DOI:	10.7150/thno.78454
Abstrakt:	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. Competing Interests: Competing Interests: Awarded patents pertaining to the results presented in the paper: J.Y. Wong, R.D. Whitaker, N. Ruiz-Opazo, and V.L.M. Herrera, PCT Application No. PCT/US2016/018417, Theranostic compositions and uses thereof, International Filing Date: Feb 18, 2016 - Assigned U.S. Patent No. 10,568,970, ISSUED February 25, 2020. Boston University holds awarded and pending patents on DEspR (dual endothelin1/VEGFsp receptor). VLMH and NRO are co-inventors on DEspR patents filed by Boston University. All other authors declare they have no competing interests. (© The author(s).)
Databáze:	MEDLINE
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