Abstract
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 NCsPLGA, NCs25% PLGA–PEG, NCs50% PLGA–PEG, NCs75% PLGA–PEG and NCs100% 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. NCsPLGA, NCs25% PLGA–PEG and NCs50% PLGA–PEG had regular spherical shape and relatively distinct boundaries compared with NCs75% PLGA–PEG and NCs100% 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. NCs50% PLGA–PEG and NCs75% PLGA–PEG had the lowest uptake by RAW 264.7 cells. In vitro, the ultrasonic gray values of NCs50% PLGA–PEG, NCs75% PLGA–PEG and NCs100% PLGA–PEG were obviously higher than those of NCsPLGA and NCs100% PLGA–PEG. NCsPLGA, NCs50% PLGA–PEG and NCs100% PLGA–PEG were injected into mice via the tail vein, but only NCs50% PLGA–PEG could produce persistent gray contrast enhancement in tumors after 24 h. Histological fluorescence of the tumor tissue confirmed that NCs50% PLGA–PEG and NCs100% 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.
Highlights
Liquid per uorocarbons (PFCs) have been used as ultrasound contrast agents (UCAs) for more than 30 years since Mattrey et al showed that per uorooctylbromide (PFOB) caused persistent enhancement of the ultrasound signal in rabbit liver.[1]
Zeta potential values were greatly reduced when Poly(lactic-co-glycolic acid) (PLGA)–polyethylene glycol (PEG) was added into the membrane material (P < 0.05)
Found for PLGA–PEG percentages ranging from 25% to 100%
Summary
Liquid per uorocarbons (PFCs) have been used as ultrasound contrast agents (UCAs) for more than 30 years since Mattrey et al showed that per uorooctylbromide (PFOB) caused persistent enhancement of the ultrasound signal in rabbit liver.[1] PFOB is stable and has low toxicity. It is the most suitable liquid per uorocarbon to be used in vivo.[2] its nanopreparations have not succeeded in the implementation of 17958 | RSC Adv., 2018, 8, 17958–17966. PEG coverage density may change the surface properties and pharmacokinetics of the nanoparticles, binding of plasma protein etc.[11,12] the effect of different PEG proportions in the shell on the NCs' biophysics and acoustics, and the NCs' ability for selective contrast enhancement have not been investigated so far
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