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Author
Fiérrez Juan, Víctor
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Abstract
With a very low survival rate, lung cancer is on top of the charts for causing the most cancer-related deaths worldwide. These numbers are expected to grow despite the wide variety of current treatments, which are not highly efficient and have huge side effects. Therefore, the development of new therapies is essential.
Thankfully, a new generation of treatments is emerging based on gene therapy. Despite the novelty of this approach, some products have already been approved and commercialized, for example, Covid-19 vaccines. Overcoming traditional therapies’ main drawbacks and the capability of targeting virtually any gene, makes this group of therapeutic agents very attractive.
Naked nucleic acids, though, are poorly suited as transfecting agents and a carrier is needed in most cases. A wide variety of passive particles have been used in the past as gene delivery vectors like viruses, liposomes, or polymeric particles. However, all of them lack the capability of crossing biological barriers among other drawbacks. Propelled particles, also called nanomotors, present an added value with its enhanced motion and diffusion. Not only the crossing capacity is improved, but also present elevated tissue penetration and increased cell transfection. More specifically, catalase-powered nanomotors have previously been investigated as chemotherapy delivery agents for lung cancer treatment. The abnormal hydrogen peroxide levels available in the tumor microenvironment make them a suitable choice for targeting this disease.
This project focuses on the validation of nanomotors’ increased gene therapy delivery due to the enhanced diffusion. Concretely, mesoporous silica nanoparticles have been loaded with siRNA using a layer-by-layer approach with polyethyleneimine and functionalized with catalase, which works as the propelling agent in the presence of hydrogen peroxide. The current work established as a proof of concept the following statement. For the first time, layer-by-layer siRNA-loaded catalase nanomotors have been assembled and their motion, biocompatibility and enhanced uptake by lung cancer cells have been demonstrated.
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