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

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 tumorfluorescence, 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.

Redox‐Responsive Polymeric Nanoparticle for Nucleic Acid Delivery and Cancer Therapy: Progress, Opportunities, and Challenges

“…[226][227][228] Based on the properties like high transverse relaxation, thermal energy conversion capacity, and Fenton reaction catalytic potential, various auxiliary function including magnetic resonance imaging (MRI)monitored biodistribution, magnetic field-guided targeted conveying can be introduced in iron oxide NPs. Nucleic acids therapy combing with MRI monitoring, [229][230][231][232][233] lncRNA therapy combing with photothermal therapy, [234] and siRNA therapy combining with Fenton-reaction therapy and MRI monitoring [235] have been reported to exert efficient multimodal nucleic acids strategy in cancer therapy. All in all, inorganic NPs have been widely used for nucleic acid delivery based on their good biocompatibility and multifunctional modifiability.…”