Details

Autor(en) / Beteiligte

• Chen, Qixian
• Qi, Ruogu
• Chen, Xiyi
• Yang, Xi
• Wu, Sudong
• Xiao, Haihua
• Dong, Wenfei

Titel

A Targeted and Stable Polymeric Nanoformulation Enhances Systemic Delivery of mRNA to Tumors

Ist Teil von

• Molecular therapy, 2017-01, Vol.25 (1), p.92-101

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• The high vulnerability of mRNA necessitates the manufacture of delivery vehicles to afford adequate protection in the biological milieu. Here, mRNA was complexed with a mixture of cRGD-poly(ethylene glycol) (PEG)-polylysine (PLys) (thiol) and poly(N-isopropylacrylamide) (PNIPAM)-PLys(thiol). The ionic complex core consisting of opposite-charged PLys and mRNA was crosslinked though redox-responsive disulfide linkage, thereby avoiding structural disassembly for exposure of mRNA to harsh biological environments. Furthermore, PNIPAM contributed to prolonged survival in systemic circulation by presenting a spatial barrier in impeding accessibility of nucleases, e.g., RNase, due to the thermo-responsive hydrophilic-hydrophobic transition behavior upon incubation at physiological temperature enabling translocation of PNIPAM from shell to intermediate barrier. Ultimately, the cRGD ligand attached to the formulation demonstrated improved tumor accumulation and potent gene expression, as manifested by virtue of facilitated cellular uptake and intracellular trafficking. These results indicate promise for the utility of mRNA as a therapeutic tool for disease treatment. [Display omitted] Chen et al. manufactured an interesting polymeric nanostructure to encapsulate the mRNA payload. The ensemble of biochemistry-based strategies in the polymeric nanostructure afforded appreciable protection to the vulnerable mRNA in the biological milieu and prompted marked gene expression at the targeted tumor cells via intravenous administration.