| Autor: |
Covarrubias-Zambrano O; Department of Chemistry, Kansas State University, Manhattan, Kansas 66506, United States., Shrestha TB; Nanotechnology Innovation Center of Kansas State, Kansas State University, Manhattan, Kansas 66506, United States.; Department of Anatomy & Physiology, Kansas State University, Manhattan, Kansas 66506, United States., Pyle M; Department of Anatomy & Physiology, Kansas State University, Manhattan, Kansas 66506, United States., Montes-Gonzalez M; Department of Chemistry, Kansas State University, Manhattan, Kansas 66506, United States., Troyer DL; Department of Anatomy & Physiology, Kansas State University, Manhattan, Kansas 66506, United States., Bossmann SH; Department of Chemistry, Kansas State University, Manhattan, Kansas 66506, United States.; Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, United States.; Drug Discovery, Delivery & Experimental Therapeutics, The University of Kansas Cancer Center, Kansas City, Kansas 66160, United States. |
| Abstrakt: |
Major concerns have arisen with respect to using viral vectors for gene therapies. Collateral effects include cancer resistance, development of new cancers, and even systemic deaths. For this reason, researchers have focused on the alternative of using nonviral nanocarriers for gene therapy. In this study, a gene delivery nanocarrier was developed, comprising a cell-penetrating peptide called WTAS as a primary nanocarrier and a poly(β-amino ester) (PBAE) polymer as a secondary nanocarrier. Here, the PBAE polymer is used to protect the WTAS peptide from early degradation while further facilitating the transportation into cells. WTAS is a peptide that penetrates cell nuclei within a few minutes after exposure, which makes it an ideal candidate to transport genetic materials. The PBAE-WTAS nanocarrier was assembled and tested against three cell lines (NSC, B16F10, and GL26). Cytotoxic studies demonstrated the relatively low toxicity of the PBAE-WTAS nanocarrier and PBAE-WTAS loaded with green fluorescent protein (GFP) plasmid DNA (pDNA@PBAE-WTAS) against all three cell lines. Cell transfection experiments were carried out using GL26 cells. These studies demonstrated a very high transfection rate of PBAE-WTAS loaded with GFP plasmid DNA, leading to virtually complete transfection (> 90%). In conclusion, we report a very promising gene delivery nanocarrier, which can be further modified to transport a variety of genetic materials for targeted therapy of multiple diseases. |
