Designing a combined targeted nano-therapy for NSCLC

Author

Moliner Usón, Tomás

Abstract

Lung cancer remains the leading cause of cancer-related mortality and can be classified into small-cell lung cancer (15% of cases) and non-small cell lung cancer (85% of cases). It can be treated with surgery only at early stages, but 70% of patients present metastasis when diagnosed. Traditionally, these patients have been treated with chemotherapy or radiotherapy. High doses of these treatments kill cancer cells with an uncontrollable damage to normal cells and an increase in drug resistance. Thus, novel targeted therapies have emerged, like specific RNA gene silencing with siRNA. Recently, combined therapy is appearing to be the most promising option to treat cancer more efficiently. In this project, we have combined the silencing effect of siRNA mTOR (inducing a gene-specific cleavage on a gene overexpressed in tumor cells) with FdU10 (novel chemotherapeutic agent). First, we have developed lysine:histidine modified pBAE nanoparticles to carry FdU10 and we have demonstrated the increase in transfection efficiency with nanoparticles and the decrease in cell viability with FdU10 transfection. We have negatively coated these nanoparticles with aspartic acid-modified pBAEs, decreasing the positive charge of the surface and thereby decreasing their spread. Later, nanoparticles were functionalized with Anisamide in order to increase the selectivity to tumor cells. An internalization assay was performed to show how functionalized nanoparticles were entering into the cell via receptor-mediated endocytosis. In conclusion, these nanoparticles have created a selective nano-delivery system for NSCLC cells. Also, we have also proved how combined therapy with siRNA mTOR and FdU10 (both complexed with the same pBAE combination) is a promising treatment and increases selectively tumor cells death.
Ex vivo hemolysis studies were performed to prove that the nanoparticles were compatible with red blood cells. In conclusion, the results of this project have demonstrated how combined therapy is a potential strategy to decrease cellular viability and how nanoparticles with Anisamide are a promising vector to deliver FdU10 and mTOR siRNA into tumor cells in a selective way.

Director

Fornaguera i Puigvert, Cristina
Borrós i Gómez, Salvador

Degree

IQS SE - Undergraduate Program in Biotechnology

Date

2021-06-21