Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα
نویسندگان
چکیده
Cervical cancer presents extremely low PEDF expression which is associated with tumor progression and poor prognosis. In this study, folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. The targeting molecule F-PEG-Chol was firstly synthesized by a novel simpler method. FLP encapsulating PEDF gene (FLP/PEDF) with a typical lipid-membrane structure were prepared by a film dispersion method. The transfection experiment found FLP could effectively transfect human cervical cancer cells (HeLa cells). FLP/PEDF significantly inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC cells) and suppressed adhension, invasion and migration of HeLa cells in vitro. In the abdominal metastatic tumor model of cervical cancer, FLP/PEDF administered by intraperitoneal injection exhibited a superior anti-tumor effect probably due to the up-regulated PEDF. FLP/PEDF could not only sharply reduce the microvessel density but also dramatically inhibit proliferation and markedly induce apoptosis of tumor cells in vivo. Moreover, the preliminary safety investigation revealed that FLP/PEDF had no obvious toxicity. These results clearly showed that FLP were desired carriers for PEDF gene and FLP/PEDF might represent a potential novel strategy for gene therapy of cervical cancer.
منابع مشابه
Cell-specific targeting by engineered M13 bacteriophage expressing VEGFR2 nanobody
Objective(s): Filamentous bacteriophage M13 was genetically engineered to specifically target mammalian cells for gene delivery purpose. Materials and Methods: A vascular endothelial growth factor receptor 2 (VEGFR2)-specific nanobody was genetically fused to the capsid gene III of M13 bacteriophage (pHEN4/3VGR19). A mammalian expression construct containing Cop-green fluorescent protein (Cop-G...
متن کاملTruncated Hepatitis B virus like nanoparticles: A novel drug delivery platform for cancer therapy
Nowadays, Nano-sized drug delivery systems have been studied extensively for theirpotential in cancer therapy. Various drug nanocarriers are being developed including liposomes, micelles, and Virus like nanoparticles (VLNPs). VLNPs offer many advantages for developing smart drug delivery systems due to their precise and repeated structures and relatively large cargo capacities. Truncated ...
متن کاملاثر نوکلئولین غشایی به عنوان یک گیرنده اختصاصی جهت دارورسانی هدفمند نانوذرات پلی لاکتیک- پلی گلایکولیک اسید حاوی داروی ضد سرطان دوکسوروبیسین و هدفمند شده با آپتامر AS1411 به سلول های سرطانی
Background & Aim: Nucleolin is one of the most abundant proteins in the nucleolus that is overexpressed on the surface of the plasmic membrane of cancer cells. It has been suggested that nucleolin is a new and promising candidate for effective targeted active-targeted delivery of nanoparticles with anti-nucleolin AS1411 aptamer (hereafter Apt), as a single-strand DNA, into a variety of hi...
متن کاملDopamine-conjugated apoferritin protein nanocage for the dual-targeting delivery of epirubicin
Objective(s): Nanocarriers are drug delivery vehicles, which have attracted the attention of researchers in recent years, particularly in cancer treatment. The encapsulation of anticancer drugs using protein nanocages is considered to be an optimal approach to reducing drug side-effects and increasing the bioavailability of anticancer drugs. Epirubicin (EPR) is an active chemotherapeutic medica...
متن کاملHSV-TK Expressing Mesenchymal Stem Cells Exert Inhibitory Effect on Cervical Cancer Model
A growing area of research is focused on cancer therapy, and new therapeutic approaches are welcomed. Mesenchymal stem cell (MSC)-based gene therapy is a promising strategy in oncology. Intrinsic tropism and migration to tumor microenvironment with off lights are attractive features of this type of cell carrier. In this way, suicide genes have also found a good platform for better performance a...
متن کامل