Nanoparticles designed to promote localized cancer regression

Experiments in rodents with carcinoma showed that with the introduction of a single dose of silver nanoparticles with subsequent irradiation, the tumor size effectively and safely decreased by 92.8%.

Scientists from the University of Pennsylvania (USA) have developed silver nanoparticles for the treatment of localized (when the tumor does not extend beyond the affected organ) cancer. The study is published in the journal Biomaterials.

The miR-148b nanoparticles have a unique chemical composition, which allows microRNAs (small non-coding RNA molecules 18-25 nucleotides long) to attach to them. As a result, miR-148b succeeds in inhibiting the messenger RNA in the cancer cell from creating the proteins necessary for the survival of the tumor.

“Despite the evidence that miRNAs are necessary for modulating oncogenesis, the main problem in the treatment of cancer is the achievement of tumor specificity and the efficient but safe delivery of miRNAs in vivo. We have developed a photoinduced silver nanoparticle nucleic acid delivery system that exhibits precise spatiotemporal control, high cellular uptake, low cytotoxicity, exit from endosomes (membrane intracellular organelle, one of the types of vesicles formed by the fusion and maturation of endocytotic vesicles. – Ed. .) and the release of functional microRNA into the liquid contents of the cell. Using this approach, we delivered miR-148b to induce apoptosis in Ras-expressing keratinocytes and squamous cell carcinoma cells in mice, while avoiding cytotoxicity in untransformed keratinocytes, ”the authors write.

As soon as the nanoparticles were concentrated in tumors in mice, researchers using light radiation with a wavelength of 415 nm separated microRNA from nanoparticles. Then, miRNA fused with messenger RNA in the cancer cell, as a result of which the mRNA ceased to produce proteins, and as a result, the cancer cell died. In approximately 20 rodent patients who were injected with a nanoparticle bound to a miRNA and then exposed to light, the cancer regressed in 24-48 hours and the tumor did not recover subsequently.

“This delivery method gives you temporal and spatial specificity,” says Adam Glick, professor of molecular toxicology and carcinogenesis. “Instead of systemic delivery of microRNAs and related side effects, you can deliver it to a specific area of ​​tissue at a specific time by exposing it to LED irradiation.” Scientists explained that miRNAs can affect different types of tissues in different ways, so there is a risk of getting undesirable side effects as a result, but delivering miRNAs to a tumor and activating it in this place reduces the likelihood of side effects and improves the effectiveness of treatment.

“A distinctive feature of our method is that miRNA can regulate a wide range of genes and is especially effective for treating heterogeneous diseases such as cancer,” added Yiming Liu, who also participated in the study. Since this treatment regimen affects several sites in the cell (microRNA can bind to various mRNAs in it), in the future it will be possible to weaken the ability of a cancer cell to become resistant to treatment.