Selective ultrasound contrast enhancement in the tumor by nanocapsules with perfluorooctylbromide: effect of PLGA-PEG proportion.

We used PLGA-COOH and PLGA-PEG-COOH blended polymer material to encapsulate perfluorooctyl bromide to prepare nanocapsules (NCs) as nano-ultrasound contrast agents. The aim of this study was to assess the effect of PLGA-PEG proportion on the physical, biological and acoustic characteristics of the nanocapsules, and to develop optimal nanocapsules for selective ultrasound contrast enhancement in tumors. The weight ratio of PLGA-PEG in the formulation was 0, 25%, 50%, 75%, and 100%, and the corresponding nanocapsules were designated NCs PLGA , NCs 25% PLGA-PEG, NCs 50% PLGA-PEG, NCs 75% PLGA-PEG and NCs 100% PLGA-PEG . As the PLGA-PEG proportion increased, the diameter and bulk modulus of the NCs gradually decreased, and the originally smooth surface of NCs was roughened. NCs PLGA , NCs 25% PLGA-PEG and NCs 50% PLGA-PEG had regular spherical shape and relatively distinct boundaries compared with NCs 75% PLGA-PEG and NCs 100% PLGA-PEG , which showed heavy agglomeration. The proportion of PLGA-PEG in the formula could also change the uptake rate of NCs by RAW 264.7 cells. NCs 50% PLGA-PEG and NCs 75% PLGA-PEG had the lowest uptake by RAW 264.7 cells. In vitro , the ultrasonic gray values of NCs 50% PLGA-PEG , NCs 75% PLGA-PEG and NCs 100% PLGA-PEG were obviously higher than those of NCs PLGA and NCs 100% PLGA-PEG . NCs PLGA , NCs 50% PLGA-PEG and NCs 100% PLGA-PEG were injected into mice via the tail vein, but only NCs 50% PLGA-PEG could produce persistent gray contrast enhancement in tumors after 24 h. Histological fluorescence of the tumor tissue confirmed that NCs 50% PLGA-PEG and NCs 100% PLGA-PEG gathered in tumor tissues. Our results indicate that the PLGA-PEG proportion in the formula is an important factor in constructing optimal nano-ultrasound contrast agents with a liquid core, and could change the nanocapsule size, surface morphology, elastic modulus, macrophage cellular uptake, and ultrasonic reflection. An appropriate PLGA-PEG proportion could help nanoparticles to achieve selective gray contrast enhancement in tumors.