Open Access

ARTICLE

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

by Liqiong Ding^1,#, Pingsheng Li^2,#, Liu He¹, Fengnan Xu¹, Jieqiong Ding^3,*, Binhua Luo^1,*

1 School of Pharmacy, Hubei University of Science and Technology, Xianning, 437100, China
2 Pharmacy Department of the Second Affiliated Hospital, Hubei University of Science and Technology, Xianning, 437100, China
3 School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning, 437100, China

* Corresponding Authors: Jieqiong Ding. Email: ; Binhua Luo. Email:

(This article belongs to the Special Issue: Polylactide Based Biopolymeric Systems)

Journal of Renewable Materials 2022, 10(3), 767-780. https://doi.org/10.32604/jrm.2022.016903

Received 07 April 2021; Accepted 29 June 2021; Issue published 28 September 2021

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.

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