title: [Feasibility of integrating tumor therapy with therapeutic effect evaluation using siRNA-loaded microbubbles].
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 ± 0.8 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.
authors.affiliation: Department of Medical Imaging, First Clinical College, Southern Medical University, Guangzhou 510515, China. E-mail: 1072134870@qq.com.
authors.forename: Shuoyang
authors.initials: S
authors.lastname: Li
authors.forename: Tinghui
authors.initials: T
authors.lastname: Yin
authors.forename: Jingguo
authors.initials: J
authors.lastname: Li
authors.forename: Bowen
authors.initials: B
authors.lastname: Zheng
authors.forename: Chen
authors.initials: C
authors.lastname: Qiu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D003287:Contrast Media; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D008081:Liposomes; D008823:Micelles; D045423:Microbubbles; D009369:Neoplasms / Q000628:therapy*; D010316:Particle Size; D011108:Polymers; D034741:RNA, Small Interfering; D056565:Sirtuin 2 / Q000235:genetics; D014465:Ultrasonics
chemical_list: D003287:Contrast Media; D008081:Liposomes; D008823:Micelles; D011108:Polymers; D034741:RNA, Small Interfering; C474199:SIRT2 protein, human; D056565:Sirtuin 2