Efficient inhibition of ovarian cancer by degradable nanoparticle-delivered survivin T34A gene

Abstract

Gene therapy has promising applications in ovarian cancer therapy. Blocking the function of the survivin protein could lead to the growth inhibition of cancer cells. Herein, we used degradable heparin–polyethyleneimine (HPEI) nanoparticles to deliver a dominant-negative human survivin T34A (hs- T34A ) gene to treat ovarian cancer. HPEI nanoparticles were characterized and were found to have a dynamic diameter of 66±4.5 nm and a zeta potential of 27.1±1.87 mV. The constructed hs- T34A gene expression plasmid could be effectively delivered into SKOV3 ovarian carcinoma cells by HPEI nanoparticles with low cytotoxicity. Intraperitoneal administration of HPEI/hs- T34A complexes could markedly inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. Moreover, according to our results, apparent apoptosis of cancer cells was observed both in vitro and in vivo. Taken together, the prepared HPEI/hs- T34A formulation showed potential applications in ovarian cancer gene therapy.

Nanoparticles co-delivering pVSVMP and pIL12 for synergistic gene therapy of colon cancer

“…The transfection efficiency of HPEI nanoparticles on the C-26 cells is comparable to that of PEI25K (p ¼ 0.29) and with less cytotoxicity than PEI25K. Those results are consistent with previous reports that HPEI could efficiently carry DNA with low cytotoxicity, 23,44 showing great promising as gene co-delivery vehicles.…”

“…HPEI nanoparticles were prepared as described previously. 23,44 Briey, 50 mg of heparin was dissolved in a MES buffer solution (100 mL, 0.05 M); then, 30 mg of NHS and 20 mg of EDC were added into the aforementioned solution to activate the carboxylic acid groups of heparin. Aer 2 h of reaction, this solution was dropped into 20 mL of PEI2K solution (7.5 mg mL À1 ) while stirring consistently at room temperature overnight.…”

Nanomedicine applications in women's health: state of the art

“…159 Degradable NPs have been used to deliver the proapoptotic survivin T34A gene and were shown to inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. 160 In addition, it has been found that Fe 3 O 4 -dextran-anti-βHCG carrying Hpa-antisense oligodeoxynucleotide has the potential to be an effective gene therapy for choriocarcinoma with significant inhibitory effects displayed on transplanted choriocarcinoma tumors in vivo. In this way, NPs can function as a harmless and effective gene vector.…”

Delivery of modified mRNA encoding vesicular stomatitis virus matrix protein for colon cancer gene therapy

“…In our previous works, delivering apoptosis-inducing genes such as VSVMP and survivin-T34A has been evaluated on several cancer models and desired therapeutic effects were achieved. [8][9][10] However, the delivery and expression efficiency of the therapeutic gene was highly restricted by the size of plasmids in certain circumstances. This always results in tremendous efforts and costs on optimizing delivery vectors.…”

“…In previous gene therapy reports including VSVMP, the effect of empty plasmid/ gene vector could be observed occasionally. 8,10,44 One possible explanation for this is that cationic agent/bacterial DNA complexes may elicit adaptive immune response under certain circumstances. 47 This phenomenon has also been observed on viral vectors.…”