US and/or MBs could be used safely to enhance the delivery of NPs loading siRNA to rat RPE-J cells. A combination of the chemical (mPEG-PLGA-PLL NPs loading siRNA) and physical (US) approaches could more effectively downregulate the mRNA and protein expression of PDGF-BB.

Abstract. The nano-microcapsules drug delivery system is currently a promising method for the treatment of many types of diseases, particularly tumors. However, the drug delivery efficiency does not reach a satisfactory level to meet treatment demands. Therefore, the effectiveness of delivery needs to be improved. Based on the alterations in the structure and modification of nano-microcapsules, ultrasound-targeted microbubble destruction (UTMD), a safe physical targeted method, may increase tissue penetration and cell membrane permeability, aiding the drug-loaded nano-microcapsules ingress the interior of targeted tissues and cells. The effectiveness and exact mechanism of action of the drug-loaded nano-microcapsules delivery system mediated by UTMD have yet to be fully elucidated. In this study, the latest advancement in UTMD-mediated drug loaded nano-microcapsules system technology was reviewed and the hindrances of UTMD-mediated drug delivery were assessed, in combination with a prospective study. The findings suggested that the drug delivery efficiency of nano-microcapsules mediated by UTMD was distinctly improved. Thus, the UTMD-mediated drug-loaded nano-microcapsules delivery system may significantly improve the efficiency of drug delivery, which may be a promising new therapeutic method.

The contrast enhanced imaging function of ultrasound contrast agents (UCAs) has been extensively investigated using physical acoustic signatures. It has a number of novel applications, including tissue‑specific molecular imaging and multi‑modal imaging. In addition there are numerous other therapeutic applications of UCAs, for example as vehicles for drug or gene delivery. These uses are discussed, as well as the acoustically‑induced biological effects, including ultrasound targeted microbubble destruction (UTMD). This review also explores the considerations for the safe use of UCA from an acoustic standpoint. The scope of the application of UCA has markedly expanded in recent years, and it is a rapidly growing field of medical research. The current article reviews recent advances in the diagnostic and therapeutic applications of ultrasound microbubble/nanobubble contrast agents.

Aim: To evaluate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) as a method for diagnosing pancreatic lesions with regard to the ductal pancreatic carcinoma and the differentiation of neoplastic from non-neoplastic lesions. Material and methods: Relevant studies published by September 6, 2015 were retrieved from PubMed, Embase, and Cochrane Central Trials databases. The articles included were mainly based on the following criteria: use of CEUS as the diagnostic tool, and the use of histology as the reference method. Two independent reviewers inspected all these papers to confirm the matching of the inclusion criteria. One reviewer with methodological expertise extracted the data from the included studies. Sensitivity, specificity and diagnostic odds ratio (DOR) were used to obtain overall estimates. Results: Eighteen studies out of 734 articles initially identified met the inclusion criteria. The primary study objective with respect to ductal adenocarcinoma was verified in 15 studies. The pooled estimate of CEUS sensitivity for the differential diagnosis of duct adenocarcinomas was 0.90 (95 % CI, 0.89-0.92), and the specificity was 0.88 (0.84-0.90). The pooled estimate for DOR was 56.38 (29.91-106.33). The area under the curve under the summary receiver operating characteristic (SROC) was 0.95. 12 out of 18 studies examined CEUS sensitivity and the average specificity with regard to the secondary study objective, distinguishing between neoplastic lesions and non-neoplastic lesions, were 0.95 (0.94-0.96) and 0.83 (0.77-0.87). The pooled estimate for DOR was 73. 25(45.31-118.43). The area under the SROC curve was 0.96. Conclusions: CEUS is a promising, reliable modality for the differential diagnosis of pancreatic adenocarcinoma in patients with pancreatic mass lesions. The presence of a hypoenhanced lesion was a sensitive predictor of pancreatic adenocarcinomas. It seems to be a useful tool in clinical practice.

A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic.

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 US-targeted microbubble destruction (UTMD) therapy using drug-loaded NCs for pancreatic cancer in vitro. In the current study, the NCs were made from the polymer nanomaterial poly(lactic-co-glycolic acid)-monomethoxypoly(ethylene glycol) (PLGA-mPEG), encapsulated with paclitaxel (PTX), to create PTX-PLGA-mPEG NCs. The PTX-PLGA-mPEG NCs were used as a US contrast agent (UCA), which produced satisfactory US contrast-enhanced images in vitro and in vivo of the rabbit kidneys, with good contrast compared with lesions in the peripheral regions. However, clear contrast-enhanced images were not obtained using PTX-PLGA-mPEG 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 PTX-PLGA-mPEG 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 PLGA-mPEG NCs and high tumor cell mortality with PTX-PLGA-mPEG NCs under US or UTMD optimal conditions. It was concluded that the use of NCs in US-mediated imaging and antitumor therapy may provide a novel application for US.

A common deletion polymorphism of the gene Bcl-2 like protein 11 (BCL2L11, BIM) has been reported to cause tyrosine kinase inhibitors (TKIs) resistance in several malignant tumors. However, the conclusions were not consistent in chronic myeloid leukemia (CML) individuals. In order to obtain a reliable conclusion, we systematically searched PubMed, Embase, Web of Science, Chinese Biomedical Database, and China National Knowledge Infrastructure and performed the meta-analysis. Six published articles contain 760 East Asian patients were identified from these electronic databases. The methodological quality of one included trial was high, and the others were moderate. Meta-analysis showed that the rate of TKI resistance between the BIM deletion and wild-type group were no statistical significance (OR = 1.24, 95% CI 0.79-1.95). In conclusion, BIM deletion may not a predictor of TKI resistance in CML individuals in East Asia.