Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2017-12-07 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To evaluate the feasibility of integrating cancer gene therapy with therapeutic effect evaluation using siRNA-loaded nano-scale microbubbles (siRNA-NBs). Methods siRNA-NBs were prepared by hetero-assembly of polymeric siRNA micelles and liposomal microbubbles, and the particle sizes and surface potentials were examined with dynamic light scattering. The distributions of cy3-labled siRNA in the tumor tissues were evaluated using confocal laser scanning microscopy. A siRNA targeting the anti-apoptosis gene SIRT2 was designed and its gene silencing effects was tested in vivo using siRNA-NBs with ultrasound exposure. The therapeutic effect of the loaded siRNA-NBs was evaluated by contrast-enhanced ultrasonography. Results The siRNA-NBs had a mean diameter of 400.7 �30.5 nm with a weak positive charge of +8.8�.8 mV. With ultrasound exposure, siRNA-NBs effectively delivered cy3-siRNA into the cytoplasm of cancer cells and caused SIRT2 suppression and cell apoptosis in tumor tissues, resulting in significantly suppressed tumor growth. In addition, contrast-enhanced ultrasonography of siRNA-NBs provided good imaging quality to allow real-time observation of blood supply during gene therapy. Conclusions As a novel ultrasound contrast agent, siRNA-NBs make possible the integration of tumor gene therapy and therapeutic effect evaluation for cancer.
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