Photochemical Internalization of siRNA for Cancer Therapy

SIMPLE SUMMARY: The objective of this review is to focus on the different nanovectors capable of transporting genetic material such as small-interfering RNA (siRNA) in order to block the expression of genes responsible for the development of cancer. Usually, these nanovectors are internalized by cancer cells via the endo-lysosomal pathway. To increase the lysosomal cargo escape, excitation using a lamp or a laser, can be applied to induce a more efficient leakage of siRNA to the cytoplasm, which is the site of action of the siRNA to block the translation of RNA into proteins. This is the mechanism of photochemical internalization. ABSTRACT: In the race to design ever more effective therapy with ever more focused and controlled actions, nanomedicine and phototherapy seem to be two allies of choice. Indeed, the use of nanovectors making it possible to transport and protect genetic material is becoming increasingly important. In addition, the use of a method allowing the release of genetic material in a controlled way in space and time is also a strategy increasingly studied thanks to the use of lasers. In parallel, the use of interfering RNA and, more particularly, of small-interfering RNA (siRNA) has demonstrated significant potential for gene therapy. In this review, we focused on the design of the different nanovectors capable of transporting siRNAs and releasing them so that they can turn off the expression of deregulated genes in cancers through controlled photoexcitation with high precision. This mechanism, called photochemical internalization (PCI), corresponds to the lysosomal leakage of the cargo (siRNA in this case) after destabilization of the lysosomal membrane under light excitation.