Tight complexation, inefficient endosomal escape and the interference with transcription process are the main causes of the low gene transfection efficiency of cationic polymer/DNA complex (polyplex) vectors. Herein, we report a novel design for a fusogenic lipidic polyplex (FLPP) vector capable of efficient dissociation triggered by intracellular reactive oxygen species (ROS) or esterase to overcome these problems. The vector's lipid layer can fuse with the cell membrane, mimicking viropexis, and eject the polyplex into the cytosol, where the cationic polymer is subsequently oxidized by ROS and becomes negatively charged, efficiently releasing the DNA. The FLPP vector avoids endosomal DNA degradation, efficiently release the DNA and does not interfere with its transcription, giving rise to high gene expression and cell transfection efficiencies. The vector is stable and long circulating in the blood, and efficiently accumulates and induces gene expression in tumors once further functionalized with the tumor-homing peptide CRGDK. The vector delivers the TRAIL gene to tumor xenografts and achieves better inhibition of tumor growth than doxorubicin with minimal toxicity.

Charge-reversal nanocarriers for cancer gene delivery

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.