Lactoferrin-Conjugated Polylactic Acid Nanobubbles Encapsulated Perfluoropentane as a Contrast Agent for Ultrasound/Magnetic Resonance Dual-Modality Imaging

Abstract

The development of contrast agents that can be activated by multiple modes is of great significance for tumor diagnosis. In this study, the lactoferrin (Lf)-conjugated polylactic acid (PLLA) nanobubbles (Lf-PLLA NBs) were used to encapsulate liquid perfluoropentane (PFP) with the double emulsion method, creating PFP loaded (PFP/ Lf-PLLA) NBs for the ultrasound/magnetic resonance dual-modality imaging of subcutaneous tumor. The particle diameter and stability of nanobubbles were investigated by photon correlation spectroscopy. The biocompatibility of nanobubbles was preliminarily evaluated by cell proliferation and migration assay, hemolysis rate, and blood biochemistry analysis. A B-mode clinical ultrasound real-time imaging system was used to perform ultrasonic imaging in vivo. Magnetic resonance imaging in vivo was applied with a clinical 3.0 T magnetic resonance imaging (MRI) scanner system. The mean particle diameter of PFP/Lf-PLLA NBs was 320.2 ± 4.1 nm with a low polydispersity index (PDI, 0.145 ± 0.025), and the NBs were negatively charged (−11.4 ± 0.4 mV). The transmission electron microscopy (TEM) results showed that PFP/Lf-PLLA NBs exhibited highly monodispersed and possessed an obvious spherical structure of nanocapsules. Nanobubbles had good stability at 4°C. Different concentrations of the PFP/Lf-PLLA NBs solution had no effect on the cell in cytotoxicity and cell migration, and the results of hemolysis rate and blood biochemistry assay also indicated the good biocompatibility of NBs. On the ultrasound/magnetic resonance imaging of tumor-bearing mice, PFP/Lf-PLLA NBs showed significantly enhanced contrast ability of tumor tissue. Therefore, PFP/Lf-PLLA NBs had great potential to be a contrast agent for tumor dual-modality imaging in vivo.

Novel Magnetic Elastic Phase-Change Nanodroplets as Dual Mode Contrast Agent for Ultrasound and Magnetic Resonance Imaging

“…Among the most commonly used polymers are PVA and PLA. Mostly polymer-based microbubbles respond at a high-frequency range upon ultrasound due to stiff shells [ 2 , 16 , 53 , 54 ]. Brismar et al synthesize incorporated salinized SPIONs and loaded them in 2% PVA solution and achieved a contrast effect in both ultrasound (5 MHz) and MRI (3 T) [ 12 ].…”

“…The majority of dual-mode contrast studies are focused on high-frequency applications, while most abdominal and cardiac examination involves 3.5 MHz frequency ultrasound [ 15 , 16 , 60 , 61 ]. In this study, microbubbles demonstrated successful enhancement at a frequency of 3.5 MHz in a 0.3 T MRI system.…”

“…Since PFH has high boiling point, MBs are responsive for HIFU applications [ 15 ]. Another study showed the successful dual-mode potential of lactoferrin conjugated PLLA PCNDs with PFP as the core gas for 10 MHz ultrasound imaging and T2 MRI [ 16 ].…”