Journal
ADVANCED SCIENCE
Volume 4, Issue 11, Pages -Publisher
WILEY
DOI: 10.1002/advs.201700324
Keywords
caveolar pathway; gene therapy; metastatic breast cancer; rod-shaped drug particles; safety
Categories
Funding
- National Natural Science Foundation of China [81673377, 81473152, 81402869]
- Natural Science Foundation of Jiangsu Province [BK20140671]
- Fostering Plan of University Scientific and Technological Innovation Team
Ask authors/readers for more resources
Efficient microRNAs (miRNA) delivery into cells is a promising strategy for disease therapy, but is a major challenge because the available conventional nonviral vectors have significant drawbacks. In particular, after these vectors are entrapped in lysosomes, the escape efficiency of genes from lysosomes into the cytosol is less than 2%. Here, a novel approach for lethal-7a (let-7a) replacement therapy using rod-shaped active pure drug nanoparticles (approximate to 130 nm in length, PNPs) with a dramatically high drug-loading of approximate to 300% as vectors is reported. Importantly, unlike other vectors, the developed PNPs/let-7a complexes (approximate to 178 nm, CNPs) can enter cells and bypass the lysosomal route to localize to the cytosol, achieving efficient intracellular delivery of let-7a and a 50% reduction in expression of the target protein (KRAS). Also, CNPs prolong the t(1/2) of blood circulation by approximate to threefold and increase tumor accumulation by approximate to 1.5-2-fold, resulting in significantly improved antitumor efficacies. Additionally, no damage to normal organs is observed following systemic injection of CNPs. In conclusion, rod-shaped active PNPs enable efficient and safe delivery of miRNA with synergistic treatment for disease. This nanoplatform would also offer a viable strategy for the potent delivery of proteins and peptides in vitro and in vivo.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available