Ultrasound contrast-enhanced imaging and in vitro antitumor effect of paclitaxel-poly(lactic-co-glycolic acid)-monomethoxypoly (ethylene glycol) nanocapsules with ultrasound-targeted microbubble destruction.

A combination of diagnostic and therapeutic ultrasound (US) techniques may be able to provide the basis of specific therapeutic protocols, particularly for the treatment of tumors. Nanotechnology may aid the progression towards the use of US for tumor diagnosis and targeted therapy. The current study investigated in vivo and in vitro US contrast imaging using nanocapsules (NCs), and also US and US­targeted microbubble destruction (UTMD) therapy using drug­loaded NCs for pancreatic cancer in vitro. In the current study, the NCs were made from the polymer nanomaterial poly(lactic­co­glycolic acid)­monomethoxypoly(ethylene glycol) (PLGA­mPEG), encapsulated with paclitaxel (PTX), to create PTX­PLGA­mPEG NCs. The PTX­PLGA­mPEG NCs were used as a US contrast agent (UCA), which produced satisfactory US contrast­enhanced images in vitro and in vivo of the rabbit kidneys, with good contrast compared with lesions in the peripheral regions. However, clear contrast­enhanced images were not obtained using PTX­PLGA­mPEG NCs as a UCA, when imaging the superficial pancreatic tumors of nude mice in vivo. Subsequently, fluorescence and flow cytometry were used to measure the NC uptake rate of pancreatic tumor cells under various US or UTMD conditions. An MTT assay was used to evaluate the efficiency of PTX and PTX­PLGA­mPEG NCs in killing tumor cells following 24 or 48 h of US or UTMD therapy, compared with controls. The specific US or UTMD conditions had been previously demonstrated to be optimal through repeated testing, to determine the conditions by which cells were not impaired and the efficiency of uptake of nanoparticles was highest. The current study demonstrated high cellular uptake rates of PLGA­mPEG NCs and high tumor cell mortality with PTX­PLGA­mPEG NCs under US or UTMD optimal conditions. It was concluded that the use of NCs in US­mediated imaging and antitumor therapy may provide a novel application for US.

Targeted delivery of biodegradable nanoparticles with ultrasound-targeted microbubble destruction-mediated hVEGF-siRNA transfection in human PC-3 cells in vitro.

A potentially viable approach for treating late-stage prostate cancer is gene therapy. Successful gene therapy requires safe and efficient delivery systems. In this study, we report the efficient delivery of small interfering RNA (siRNA) via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers. On the basis of previous findings, cyclic Arg-Gly-Asp (cRGD) peptides were conjugated to NPs to recognize the target site, integrin αvß3, expressed in high levels in PC-3 prostate cancer cells. The suppression of angiogenesis by the downregulation of vascular endothelial growth factor (VEGF) expression has been widely used to inhibit the growth of malignant tumors. In our study, human VEGF (hVEGF)-siRNA was encapsulated in NPs to inhibit VEGF expression in PC-3 cells. Concurrently, sonoporation induced by ultrasound-targeted microbubble destruction (UTMD) was utilized for the delivery of siRNA-loaded NPs. Our results showed low cytotoxicity and high gene transfection efficiency, demonstrating that the targeted delivery of biodegradable NPs with UTMD may be potentially applied as new vector system for gene delivery.

Enhancing HSP70-ShRNA transfection in 22RV1 prostate cancer cells by combination of sonoporation, liposomes and HTERT/CMV chimeric promoter.

Gene therapy is a potentially viable approach for treating hormone-refractory prostate cancer (HRPC), it requires efficient delivery systems and a target gene. Inducing carcinoma cell apoptosis by inhibition of heat shock protein 70 (HSP70) overexpression has been emerging as an attractive strategy for cancer therapy. In our study, the high tumor-specificity of human telomerase reverse transcriptase (HTERT) expression prompted the use of an HTERT/cytomegalovirus (CMV) chimeric promoter to drive HSP70-ShRNA expression to induce HRPC 22RV1 cell apoptosis. At the same time, sonoporation induced by ultrasound-targeted microbubble destruction (UTMD) was utilized for delivery of plasmid loaded with HTERT/CMV promoter. Our results indicated the combination of sonoporation, low-dose liposomes and HTERT/CMV chimeric promoter as a delivery system has the potential to promote efficient gene transfer with lower cytotoxicity.