MIRNANO · Multifunctional miRNA-targeting nanodevices for pluripotent cancer theranostics

Multifunctional miRNA-targeting nanodevices for pluripotent cancer theranostics

“MIRNANO” is a multidisciplinary program at the forefront of nanotechnology and nanomedicine. The foundation of the project is the combination of materials chemistry and biomolecular (DNA/RNA) engineering, aiming to develop innovative technologies that can all contribute to advancing the field of bionanotechnology and personalized medicine. • Nanotechnology has revolutionized modern research and has led to unparalleled achievements in a plethora of fields, including biomedicine and bioengineering. • MiRNAs are short endogenous noncoding RNAs that regulate gene expression at the post-transcriptional level. There is established evidence that aberrant expression of certain miRNAs (oncomiRs) is associated with cancer. Therefore, miRNAs have emerged as promising targets for silencing-based anticancer therapies (anti-miR) and as biomarkers for early diagnosis. • Nucleic acid engineering can improve in vivo stability of molecular drugs by using new classes of nucleic acid structures or artificial oligonucleotide mimics and provide intelligent systems by designing programmable DNA nanodevices. • Delivery systems are needed to provide efficient release of nucleic acids, improve bioavailability, biocompatibility and reduce off-target effects. Porous silicon nanoparticles (pSiNPs) present tunable pore sizes, allow for control of their physicochemical properties and show a biocompatible degradation pathway in vivo. Objectives: 1) develop novel cancer therapeutics for precision nanomedicine leveraging silencing of oncogenic microRNAs; 2) fabricate innovative hybrid technologies allowing for detection and imaging of target microRNAs in real time; 3) design advanced DNA nanodevices responsive to biomolecular inputs for theranostics. The research work has generated the following outputs: 1. The development of novel therapeutics for ovarian cancer based on tumor-targeting, microRNA-silencing porous silicon nanoparticles (pSiNPs).This was achieved by using biodegradable porous silicon nanoparticles loaded with specific anti-miR artificial oligonucleotides and decorated with tumor-targeting ligands (ACS Appl. Mater. Interfaces 2019, 11, 27, 23926-23937). 2. The fabrication of a nano-in-nano platform housing miRNA-responsive dynamic DNA nanodevices incorporated into a hybrid polymer/porous silicon scaffold for sensing of miRNA markers in situ and in real time (Nanoscale, 2020,12, 2333-2339). 3. The manufacturing of tissue engineering scaffolds made from biocompatible polymers aimed to provide physical cues to direct the extension of neurites and to encourage repair of damaged nerves. This has been accomplished by including neurotrophic payloads in the scaffold to substantially enhance regrowth and repair processes. The nanofiber hybrids were demonstrated to increase neurite extension relative to drug-free control nanofibers in a dorsal root ganglion explant assay. 4. The design of programmable DNA-based transducers responding to biomolecular inputs for the actuation of synthetic theranostic molecular networks.This has been carried out by designing, developing and testing nucleic acid based-networks, including DNA/RNA strand displacement reactions and activation of functional RNAs, controlled by oncogenic transcription factors through rationally designed DNA actuators.

Data: CORDIS, © European Union