Abstract:Abstract. The aim of the present study was to investigate whether ultrasound combined with microbubbles was able to enhance liposome-mediated transfection of genes into human prostate cancer cells, and to examine the association between autophagy and tumor protein P53 (P53). An MTT assay was used to evaluate cell viability, while flow cytometry and fluorescence microscopy were used to measure gene transfection efficiency. Autophagy was observed using transmission electron microscopy. Reverse transcription-poly… Show more
“…The mechanism by which sonoporation enhances the sensitivity of chemotherapy relies on a cavitation effect and a mechanical effect ( 14 - 16 ). The sonoporation effect occurs by means of the characteristics of microbubbles under different mechanical indexes (MIs) ( 17 - 19 ).…”
ObjectiveTo explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.MethodsFrom October 2014 to June 2016, twelve patients volunteered to participate in this study. Eleven patients had hepatic metastases from tumors of the digestive system, and one patient had pancreatic carcinoma. According to the mechanical index (MI) in the ultrasound field, patients were classified into four groups with MIs of 0.4, 0.6, 0.8 and 1.0. Within half an hour after chemotherapy, patients underwent ultrasound scanning with ultrasound microbubbles (SonoVue) to enhance the efficacy of chemotherapy. All adverse reactions were recorded and were classified in 4 grades according to the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE V4.03). Tumor responses were evaluated by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria. All the patients were followed up until progression.ResultsAll the adverse reactions recorded were level 1 or level 2. No local pain occurred in any of the patients. Among all the adverse reactions, fever might be related to the treatment with ultrasound combined with microbubbles. Six patients had stable disease (SD), and one patient had a partial response (PR) after the first cycle of treatment. At the end of follow-up, tumor progression was restricted to the original sites, and no new lesions had appeared.ConclusionsOur preliminary data showed the potential role of a combined treatment with ultrasound and microbubbles in enhancing the chemotherapeutic sensitivity of malignant tumors of the digestive system. This technique is safe when the MI is no greater than 1.0.
“…The mechanism by which sonoporation enhances the sensitivity of chemotherapy relies on a cavitation effect and a mechanical effect ( 14 - 16 ). The sonoporation effect occurs by means of the characteristics of microbubbles under different mechanical indexes (MIs) ( 17 - 19 ).…”
ObjectiveTo explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.MethodsFrom October 2014 to June 2016, twelve patients volunteered to participate in this study. Eleven patients had hepatic metastases from tumors of the digestive system, and one patient had pancreatic carcinoma. According to the mechanical index (MI) in the ultrasound field, patients were classified into four groups with MIs of 0.4, 0.6, 0.8 and 1.0. Within half an hour after chemotherapy, patients underwent ultrasound scanning with ultrasound microbubbles (SonoVue) to enhance the efficacy of chemotherapy. All adverse reactions were recorded and were classified in 4 grades according to the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE V4.03). Tumor responses were evaluated by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria. All the patients were followed up until progression.ResultsAll the adverse reactions recorded were level 1 or level 2. No local pain occurred in any of the patients. Among all the adverse reactions, fever might be related to the treatment with ultrasound combined with microbubbles. Six patients had stable disease (SD), and one patient had a partial response (PR) after the first cycle of treatment. At the end of follow-up, tumor progression was restricted to the original sites, and no new lesions had appeared.ConclusionsOur preliminary data showed the potential role of a combined treatment with ultrasound and microbubbles in enhancing the chemotherapeutic sensitivity of malignant tumors of the digestive system. This technique is safe when the MI is no greater than 1.0.
“…Hence, this study examined the sonoporation effect on molecules ranging from 1.2 kDa up to 70 kDa. This size range corresponds to materials such as chemotherapeutic drugs and drug carriers (1–70 kDa), siRNA (∼14 kDa) and proteins (3–40 kDa) ( Maciulevičius et al, 2022 ; Liu et al, 2019 ; Dreher et al, 2006 ; Matsunaga et al, 2018 ; Wang et al, 2016 ; Tsai et al, 2012 ; Tian et al, 2020 ; Delalande et al, 2013 ; Huang et al, 2017 ; Marmottant et al, 2005 ). Fig.…”
“…Ultrasound as a physical vector may be more attractive than previous chemical approaches from a clinical viewpoint [7,8]. Herein, USMB was considered to be a ‘gentle’ technique compared with various other drug delivery systems [9]. A number of studies have focused on how USMB could enhance the delivery efficiency of chemotherapeutics [10,11].…”
Section: Introductionmentioning
confidence: 99%
“…Through these pores, drugs, gene products, and some other particles can enter the cells [14–16]. This phenomenon has been demonstrated by high-speed camera images [9]. A correlative study also suggested that the increase of membrane permeability was enhanced by sonoporation [17].…”
BackgroundUltrasound/microbubble (USMB)-mediated sonoporation is a new strategy with minimal procedural invasiveness for targeted and site-specific drug delivery to tumors. The purpose of this study was to explore the effect of different breast cancer cell lines on sonoporation efficiency, and then to identify an optimal combination of USMB parameters to maximize the sonoporation efficiency for each tumor cell line.Material/MethodsThree drug-sensitive breast cell lines – MCF-7, MDA-MB-231, and MDA-MB-468 – and 1 multidrug resistance (MDR) cell line – MCF-7/ADR – were chosen. An orthogonal array experimental design approach based on 3 levels of 3 parameters (A: microbubble concentration, 10%, 20%, and 30%, B: sound intensity, 0.5, 1.0, and 1.5 W/cm2, C: irradiation time, 30, 60, and 90 s) was employed to optimize the sonoporation efficiency.ResultsThe optimal USMB parameter combinations for different cell lines were diverse. Under optimal parameter combinations, the maximum sonoporation efficiency differences between different breast tumor cell lines were statistically significant (MDA-MB-231: 46.70±5.79%, MDA-MB-468: 53.44±5.69%, MCF-7: 59.88±5.53%, MCF-7/ADR: 65.39±4.01%, P<0.05), so were between drug-sensitive cell line and MDR cell line (MCF-7: 59.88±5.53%, MCF-7/ADR: 65.39±4.01%, p=0.026).ConclusionsDifferent breast tumor cell lines have their own optimal sonoporation. Drug-resistant MCF-7/ADR cells had higher sonoporation efficiency than drug-sensitive MCF-7 cells. The molecular subtype of tumors should be considered when sonoporation is applied, and optimal parameter combination may have the potential to improve drug-delivery efficiency by increasing the sonoporation efficiency.
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