Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome.

Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to the tumor even in the presence of anti-viral Nabs could be gold nanoparticles able to transfer DNA molecules. However, the ability of these nanoparticles to carry large DNA molecules, such as an oncolytic adenovirus genome, has not been studied. In this work, gold nanoparticles were functionalized with different amounts of polyethylenimine to transfer in a safe and efficient manner a large oncolytic virus genome. Their transfer efficacy and final effect of the oncolytic virus in cancer cells are studied. For each synthesized nanoparticle, (a) DNA loading capacity, (b) complex size, (c) DNA protection ability, (d) transfection efficacy and (e) cytotoxic effect were studied. We observed that small gold nanoparticles (70-80 nm in diameter) protected DNA against nucleases and were able to transfect the ICOVIR-15 oncolytic virus genome encoded in pLR1 plasmid. In the present work, efficient transgene RNA expression, luciferase activity and viral cytopathic effect on cancer cells are reported. These results suggest gold nanoparticles to be an efficient and safe vector for oncolytic adenovirus genome transfer.

Computed tomographic angiography with VirSSPA three-dimensional software for perforator navigation improves perioperative outcomes in DIEP flap breast reconstruction.

BACKGROUND: Vascular anatomy of the abdominal wall varies greatly, especially in the case of the perforator branches of the deep inferior epigastric artery. Preoperative three-dimensional reconstructions with VirSSPA software have been used in the authors' center since the year 2007 for the planning of perforator flaps in breast reconstruction. The main objectives were to reduce surgery time and the number of complications. METHODS: A comparative study was conducted in 70 patients subjected to delayed breast reconstruction based on unilateral deep inferior epigastric perforator (DIEP) flaps. Half of the patient group underwent preoperative imaging with computed tomographic angiography-guided VirSSPA reconstruction, whereas the other half was subjected to preoperative Doppler ultrasound for perforator mapping. Operation time ranges, lengths of stay, and operative complications were assessed. RESULTS: The use of VirSSPA preoperative planning correlated with operative times reduced by a mean of 2 hours 8 minutes. In addition, a statistically significant reduction (>45 percent) in the incidence of any flap-related complications was observed in patients undergoing preoperative computed tomographic angiography-guided VirSSPA reconstruction and a decrease above 50 percent in overall donor-site morbidity. The use of computed tomographic angiography-guided VirSSPA three-dimensional reconstruction was found to be a protective factor against developing any kind of complication after DIEP flap surgery (odds ratio, 0.03; 95 percent confidence interval, 0.006 to 0.15). CONCLUSIONS: Computed tomographic angiography-guided VirSSPA three-dimensional reconstruction in the assessment of perforator flaps was proved to be safe and reliable. The main benefits of this technique were the reduction of surgical time and reduction of the number of complications.

Use of a three-dimensional virtual reality model for preoperative imaging in DIEP flap breast reconstruction.

BACKGROUND: The significant variation in the vascular anatomy of the abdominal wall makes preoperative imaging essential when raising a deep inferior epigastric artery perforator (DIEP) flap due to the potential for maximizing operative success, reducing intraoperative error and minimizing operative complications. Computerized models and virtual reality applications are being used to facilitate teaching and preoperative evaluation in a number of other complex anatomical regions. The variability in perforator anatomy makes DIEP flap surgery a suitable candidate for application of such technology. In this context, a study was undertaken to determine the feasibility of computed tomography angiography (CTA)-guided VirSSPA three-dimensional (3D) software for virtual reality navigation in DIEP flap surgery and to compare findings with operative measurements. MATERIALS AND METHODS: We recruited 12 consecutive patients planned for an elective DIEP flap for breast reconstruction. Each patient underwent preoperative imaging of the anterior abdominal wall vasculature with both conventional CTA and VirSSPA 3D reconstruction. Imaging findings were compared with operative findings. RESULTS: In all cases, the major perforators were accurately localized using both methods. 3D reconstruction of the abdominal wall with VirSSPA demonstrated a significant good correlation with perforator location compared with operative findings, showing an average error rate of 0.23cm (95% CI, 0.17-0.30). CONCLUSION: In short, the main advantage of VirSSPA, when used in conjunction with an image assessment such as CTA, is to provide additional and potentially more accurate data over conventional CTA with regard to the site of the best perforators and its course through the muscle.