Ultrasound-Guided Delivery of siRNA and a Chemotherapeutic Drug by Using Microbubble Complexes: In Vitro and In Vivo Evaluations in a Prostate Cancer Model

Content Provider	Semantic Scholar
Author	Bae, Yun Jung Yoon, Young Il Yoon, Tae-Jong Lee, Hak Jong
Copyright Year	2016
Abstract	OBJECTIVE To evaluate the effectiveness of ultrasound and microbubble-liposome complex (MLC)-mediated delivery of siRNA and doxorubicin into prostate cancer cells and its therapeutic capabilities both in vitro and in vivo. MATERIALS AND METHODS Microbubble-liposome complexes conjugated with anti-human epidermal growth factor receptor type 2 (Her2) antibodies were developed to target human prostate cancer cell lines PC-3 and LNCaP. Intracellular delivery of MLC was observed by confocal microscopy. We loaded MLC with survivin-targeted small interfering RNA (siRNA) and doxorubicin, and delivered it into prostate cancer cells. The release of these agents was facilitated by ultrasound application. Cell viability was analyzed by MTT assay after the delivery of siRNA and doxorubicin. Survivin-targeted siRNA loaded MLC was delivered into the xenograft mouse tumor model. Western blotting was performed to quantify the expression of survivin in vivo. RESULTS Confocal microscopy demonstrated substantial intracellular uptake of MLCs in LNCaP, which expresses higher levels of Her2 than PC-3. The viability of LNCaP cells was significantly reduced after the delivery of MLCs loaded with siRNA and doxorubicin (85.0 ± 2.9%), which was further potentiated by application of ultrasound (55.0 ± 3.5%, p = 0.009). Survivin expression was suppressed in vivo in LNCaP tumor xenograft model following the ultrasound and MLC-guided delivery of siRNA (77.4 ± 4.90% to 36.7 ± 1.34%, p = 0.027). CONCLUSION Microbubble-liposome complex can effectively target prostate cancer cells, enabling intracellular delivery of the treatment agents with the use of ultrasound. Ultrasound and MLC-mediated delivery of survivin-targeted siRNA and doxorubicin can induce prostate cell apoptosis and block survivin expression in vitro and in vivo.
Starting Page	497
Ending Page	508
Page Count	12
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://kjronline.org/Synapse/Data/PDFData/0068KJR/kjr-17-497.pdf
PubMed reference number	27390541v1
Alternate Webpage(s)	https://doi.org/10.3348/kjr.2016.17.4.497
DOI	10.3348/kjr.2016.17.4.497
Journal	Korean journal of radiology
Volume Number	17
Language	English
Access Restriction	Open
Subject Keyword	Apoptosis Cultured Cell Line Epidermal Growth Factor Receptor Evaluation Growth Factor Receptors Immunostimulating conjugate (antigen) Leukemia, B-Cell Liposomes Malignant neoplasm of prostate Microbubbles Microscopy, Confocal Non-Small Cell Lung Carcinoma Prostate carcinoma Prostatic Neoplasms RNA RNA, Small Interfering Western Blotting Xenograft type of graft cancer cell doxorubicin hydrochloride liposome monooxyethylene trimethylolpropane tristearate
Content Type	Text
Resource Type	Article