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.