Aptamers are single-stranded nucleic acids that bind to proteins and small molecules with high affinity by folding into a three-dimensional conformation. The clinical progression of therapeutic aptamers is hindered by several challenges, particularly concerning nuclease degradation, limited endosomal escape ability, and low effective intracellular delivery. BioSilicaThera (n. ECS00000017) aims to develop a biomarker-responsive hybrid Aptamer-Silica nanoparticle (Apt-SiNP) platform for theranostic applications. This platform will enable controlled degradation of silica NPs in response to overexpressed biomarkers (i.e. onco-miRNA), and consequent release of functional aptamers in the cytosol of cancer cells. Leveraging previous success from our network in supramolecular nucleic acid (NA)-based organosilica NPs, the project’s scientific goals include designing breakable Apt-SiNPs and delivering functional aptamers with therapeutic activity upon specific biomolecular interactions serving as a trigger input.

The challenges we wish to address are:

1. Designing biomarker-responsive Apt-SiNPs using the molecular programmability of oligonucleotides.
2. Delivering functional aptamers alongside Apt-SiNP degradation.
3. Activating therapeutic functions in response to interactions with biomarkers inside the cells.
4. Demonstrating the targeting capability and the therapeutic efficacy of the designed aptamers in human lung cancer cells and organoids in vitro.

The nanomaterials will be designed on one hand to incorporate the aptamer directly in the silica framework, but also, as an alternative, to decorate very small porous cage-like silica NPs. The small size of these NPs could potentially facilitate the development of intravenous delivery methods, whereas larger nanoparticles might be suitable for formulations administered via the intranasal route. BioSilicaThera anticipates significant advancements in smart nanomaterials for cancer theranostics, enhancing NA delivery in tumor models.