Abstract
BackgroundEffective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy.ResultsHerein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration.ConclusionsThis study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.
Highlights
Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy
Preparation and characterization of the protein liposomes In this study, the liposome was prepared by physically assembling method (Fig. 1a), the amphiphilic protein derivative modified by glycidyl hexadecyl dimethylammonium chloride (GHDC) is different from the conventional protein-modified nanospheres or liposomes
The morphology of GL/AChE and Tf-PL/AChE was analyzed by transmission electron microscopy (TEM) (Fig. 2a, b)
Summary
Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. More than 1500 cancer gene therapy programs have been confirmed for global clinical trials [11,12,13]. Therapeutic genes such as DNA and siRNA are degraded by enzymes in the blood, tissue or cytoplasm during transmission, and the biological half-life is very short [14, 15]. Developing efficient gene delivery systems remains the biggest challenge for gene therapy [19, 20]. Low cytotoxicity, simple preparation, low cost, good safety, strong tumor
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