Tumor-Penetrating Peptide-Functionalized Redox-Responsive Hyperbranched Poly(amido amine) Delivering siRNA for Lung Cancer Therapy
2018
Bio-safety and the targeting ability of gene delivery systems are critical aspects for gene therapy of cancer. In this study, we report the synthesis and use of redox-responsive poly(amido amine) (PAA) with good biocompatibility and biodegradation as a gene carrier material. A tumor-specific tissue penetration peptide, internalizing-RGD (iRGD) was then conjugated to PAA with an amidation reaction. In experiments using H1299 cells, PAA-iRGD was found to have a lower cytotoxicity and higher cellular uptake efficiency, compared to PAA. An siRNA, specific to epidermal growth factor receptor (EGFR) that is over-expressed on the lung cancer cell surface and often targeted in lung cancer treatment, was designed to silence EGFR (i.e., siEGFR) for delivery by the gene carrier PAA-iRGD. EGFR gene silencing, apoptosis, anti-proliferation, and anti-tumor effects of PAA-iRGD/siEGFR were evaluated in vitro and in vivo. PAA-iRGD/siEGFR displayed a much higher gene silencing ability compared to PAA and polyethyleneimine ...
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