Amphiphilic and Perfluorinated Poly(3-Hydroxyalkanoate) Nanocapsules for 19F Magnetic Resonance Imaging

Nanoparticles have recently emerged as valuable tools in biomedical imaging techniques. Here PEGylated and fluorinated nanocapsules based on poly(3-hydroxyalkanoate) containing a liquid core of perfluorooctyl bromide PFOB were formulated by an emulsion-evaporation process as potential 19F MRI imaging agents. Unsaturated poly(hydroxyalkanoate), PHAU, was produced by marine bacteria using coprah oil and undecenoic acid as substrates. PHA-g-(F; PEG) was prepared by two successive controlled thiol-ene reactions from PHAU with firstly three fluorinated thiols having from 3 up to 17 fluorine atoms and secondly with PEG-SH. The resulting PHA-g-(F; PEG)-based PFOB nanocapsules, with a diameter close to 250–300 nm, are shown to be visible in 19F MRI with an acquisition time of 15 min. The results showed that PFOB-nanocapsules based on PHA-g-(F; PEG) have the potential to be used as novel contrast agents for 19F MRI.

Preparation of Hollow Silica Nanoparticles Using Fluorinated Surfactant and Fluorocarbon Solvents

In this study, we used a new class of fluorinated surfactant as a soft template for the preparation of the hollow silica nanoparticles. The size of the hollow silica nanoparticles was enlarged by incorporating a variety of swelling agents (perfluorodecalin, perfluorotributylamine, perfluorooctane, and perfluorooctyl bromide) into the cores of the micelles of the fluorinated surfactant. However, once we used the perfluorinated acids (perfluorooctadecanoic acid and perfluorodecanoic acid) as swelling agents, the structure of silica nanoparticles is solid without the formation of hollow voids. The TEM analysis combined with copper elemental mapping of the hollow silica loaded with copper hexadecafluorophthalocyanine indicated that the cores of the hollow silica nanoparticles are hydrophobic. The formation mechanism of the hollow silica nanoparticles is similar to that prepared by hydrocarbon surfactant/hydrocarbon, which was supported by the zeta potential measurements. The prepared hollow silica nanoparticles had the type IV isotherm with the H3 hysteresis loop.

Silica nanoparticle coated perfluorooctyl bromide for ultrasensitive MRI

MRI with hyperpolarized 129Xe can achieve low-concentration detection.

Thin-Shelled PEGylated Perfluorooctyl Bromide Nanocapsules for Tumor-Targeted Ultrasound Contrast Agent

Shell thickness determines the acoustic response of polymer-based perfluorooctyl bromide (PFOB) nanocapsule ultrasound contrast agents. PEGylation provides stealth property and arms for targeting moieties. We investigated a modulation in the polymer formulation of carboxy-terminated poly(D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide-co-glycolide)-block-polyethylene glycol (PLGA-b-PEG) to produce thin-shelled PFOB nanocapsules while keeping its echogenicity, stealth property, and active targeting potential. Polymer formulation contains 40% PLGA-PEG that yields the PEGylated PFOB nanocapsules of approximately 150 nm size with average thickness-to-radius ratio down to 0.15, which adequately hindered phagocytosis. Functionalization with antibody enables in vitro tumor-specific targeting. Despite the acoustic response improvement, the in vivo tumor accumulation was inadequate to generate an observable acoustic response to the ultrasound power at the clinical level. The use of PLGA and PLGA-PEG polymer blend allows the production of thin-shelled PFOB nanocapsules with echogenicity improvement while maintaining its potential for specific targeting.

Carboxyl of Poly(D,L-lactide-co-glycolide) Nanoparticles of Perfluorooctyl Bromide for Ultrasonic Imaging of Tumor

Perfluorooctyl bromide (PFOB) enclosed nanoparticles (NPs) as ultrasonic contrasts have shown promising results in the recent years. However, NPs display poor contrast enhancement in vivo. In this work, we used the copolymers poly(lactide-co-glycolide) carboxylic acid (PLGA-COOH) and poly(lactide-co- glycolide) poly(ethylene glycol) carboxylic acid (PLGA-PEG-COOH) as a shell to encapsulate PFOB to prepare a nanoultrasonic contrast agent. The NPs were small and uniform (210.6±2.9 nm with a polydispersity index of 0.129±0.016) with a complete shell nuclear structure under the transmission electron microscopy (TEM). In vitro, when concentration of NPs was ≥10 mg/ml and clinical diagnostic frequency was ≥9 MHz, NPs produced intensive enhancement of ultrasonic gray-scale signals. NPs could produce stable and obvious gray enhancement with high mechanical index (MI) (MI > 0.6). In vivo, the NPs offered good ultrasound enhancement in tumor after more than 24 h and optical imaging also indicated that NPs were mainly located at tumor site. Subsequent analysis confirmed that large accumulation of fluorescence was observed in the frozen section of the tumor tissue. All these results caused the conclusion that NPs encapsulated PFOB has achieved tumor-selective imaging in vivo.

End-chain fluorination of polyesters favors perfluorooctyl bromide encapsulation into echogenic PEGylated nanocapsules

Fluorination of polyesters favors the encapsulation efficiency of perfluorooctyl bromide into nanocapsules.