Design of targeted nanoparticles for modulating oncogene expression in NSCLC

Author

Olmo Osuna, Laura

Abstract

Non-Small cell lung cancer accounts for approximately 80% of all cases of lung cancer and has become the leading cause of cancer-related death. Combination chemotherapy is the treatment of choice but unfortunately the 70% of the patients are diagnosed at an advantage stage and present metastatic disease at the moment of diagnosis, thus making current treatment inefficacious. For this reason, new treatment modalities have emerged in the last years, like RNA mediated gene silencing using small interfering RNA (siRNA). To explore the potential of siRNA therapy for NSCLC, we have developed Anisamide-targeted nanoparticles composed of Poly(β-aminoesters)s (pBAE) to effectively deliver siRNA into sigma receptor-expressing NSCL cells. First, pBAE nanoparticles were modified as to decrease the promiscuity of the lysine: histidine-terminated complex. To do so, the particles have been coated with negative pBAE, as to decrease the positive charge of the surface. Then this negative pBAE was functionalized with Anisamide in order to increase the selectivity of the nanoparticles. The resulting nanoparticles were slightly positive (15 mV) and less than 200 nm in size and the stability of the coating was maintain during the time. The electrostatic interaction between positive and negative polymer has make the nanoparticle more stable.
Nanoparticles formulation here have showed an increase in the transfection efficiency as compared with those without Anisamide. The internalization assay showed that nanoparticles were entering into the cell via receptor-mediated endocytosis, then a more specific systems was achieved.
In conclusion, our results demonstrate that the modified pBAE nanoparticles with Anisamide is a promising vector to delivery siRNA into tumors more efficient and selectively and this is potentially a valid therapeutic modality in the gene therapy of human NSCLC.

 

Director

Borrós i Gómez, Salvador
Fornaguera Puigvert, Cristina 

Degree

IQS SE - Master’s Degree in Bioengineering

Date

2020-06-30