Ultrasound contrast-enhanced imaging and in vitro antitumor effect of paclitaxel-poly(lactic-co-glycolic acid)-monomethoxypoly (ethylene glycol) nanocapsules with ultrasound-targeted microbubble destruction

Abstract

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.

UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy

“…After the cells reached 60-70% confluence, the cells were trypsinized and collected in a tube preloaded with FITC in PBS to have a final concentration of 2 mg/mL for each sample. Then, according to our previous study, SonoVue microbubbles were added into each cell suspension to a concentration of 20% (v/v) 45 . The tube filled with a total of 2 mL mixed suspension was fixed in the tank at room temperature (Fig.…”

“…For the Gem-Au DENPs/miR-21i + U group, the US transducer (PHYSIOSON-Basic, PHYSIOSON Elektro-medizin, Germany) was positioned above the tumor, and SonoVue (1.18 mg/mL, in 0.2 mL saline) was slowly injected via tail vein after intratumoral injection of Gem-Au DENPs/miR-21i polyplexes. According to a previous study, the tumors were insonated percutaneously for 2 min to achieve the longest active sonoporation time (1 MHz, 0.4 W/cm 2 , 20% microbubbles) 45 , 46 .…”

“…It also has been proven that UTMD can enhance the clathrin-based endocytosis of nanoparticles (NPs) 44 . In our previous study, we have also shown that under a UTMD condition, the delivery of paclitaxol (PTX) by methoxy polyethylene glycol-polylacticco-glycolicacid-polylysine ( m PEG-PLGA-PLL) NPs can be enhanced for tumor chemotherapy 45 , 46 .…”

Ultrasound-targeted microbubble destruction improves the suppression and magnetic resonance imaging of pancreatic cancer with polyethyleneimine nanogels

“…UTMD is expected to provide a safe and effective technical means for the sensitization of pancreatic cancer chemotherapy 30 . Therefore, this approach could revolutionize the treatment of pancreatic cancer by breaking the tough interstitial barrier, reducing structural obstacles, and supporting efficient delivery of chemotherapeutic vectors 31 , 32 .…”

The use of 5-fluorouracil-loaded nanobubbles combined with low-frequency ultrasound to treat hepatocellular carcinoma in nude mice

“…The UTMD technique involves extensively irradiating drug-loaded microbubbles with ultrasonic pulses at the proper energy level when the microbubbles reach the target tissues via the blood stream after peripheral intravenous injection. The “cavitation effect” and “mechanical effect” produced by ultrasonic irradiation can destroy the cell membrane and enhance cell membrane permeability [ 9 – 11 ], promoting the amount of drug that enters the target tissues (Fig. 1 ).…”