title: Biologically responsive carrier-mediated anti-angiogenesis shRNA delivery for tumor treatment.
abstract: Small interfering RNA (siRNA) has increased the hope for highly-efficient treatment of gene-related diseases. However, the stable and efficient delivery of therapeutic nucleic acids is a prerequisite for the successful clinical translation of RNA interfering therapy. To achieve this, we condensed the low molecular weight polyethyleneimine (PEI, Mw < 2000) with 2,6-pyridinedicarboxaldehyde (PDA) to synthesize a biologically responsive and degradable cationic polymer (abbreviated to PDAPEI) which was utilized as a gene vector for the delivery of a VEGF-A shRNA expression plasmid DNA (pDNA). The resulting electrostatic interaction between PDAPEI and pDNA led to the self-assembly of nanoscale polyplexes with suitable particle size and stable zeta potential. The PDAPEI/pDNA polyplexes demonstrated an outstanding gene transfection and silencing efficiency at 30 w/w ratio, as well as negligible cytotoxicity. Also, the designed polymer showed no stimulation to the innate immune system. Moreover, compared with PEI 25 KDa, the polyplexes accomplished comparatively better anti-angiogenesis efficacy, which resulted in the inhibition of tumor growth in subcutaneous tumor mice models. In conclusion, PDAPEI has great potential to be a gene delivery vector for cancer therapy.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Che
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Anqi
authors.initials: A
authors.lastname: Tao
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Shun
authors.initials: S
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Weien
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001688:Biological Products / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D020868:Gene Silencing; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010957:Plasmids; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy*; D014162:Transfection; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D004337:Drug Carriers; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A