Nanobubbles with a size less than 1 μm could make a promising application in ultrasound molecular imaging and drug delivery. However, the fabrication of stable gas encapsulation nanobubbles is still challenging. In this study, a novel method for preparation of lipid- encapsulated nanobubbles was reported. The dispersed phospholipid molecules in the prefabricated free nanobubbles solution can be assembled to form controllable stable lipid encapsulation gas-filled ultrasound-sensitive liposome (GU-Liposome). The optimized preparation parameters and formation mechanism of GU-Liposome were investigated in detail. Results showed that this type of GU-Liposome had mean diameter of 194.4 ± 6.6 nm and zeta potential of -25.2 ± 1.9 mV with layer by layer self-assembled lipid structure. The acoustic imaging analysis in vitro indicated that ultrasound imaging enhancement could be acquired by both perfusion imaging and accumulation imaging. The imaging enhancement level and duration time was related with the ratios of lipid to gas in the GU-Liposome structure. All in all, by this novel and controllable nanobubble construction technique, it will broaden the future theranostic applications of nanobubbles.

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Uniform and multifunctional poly(lactic acid) (PLA)-nanoparticle composite has enormous potential for applications in biomedical and materials science. A detailed understanding of the surface and interface chemistry of these composites is essential to design such materials with optimized function. Herein, we designed and investigated a simple PLA-magnetic nanoparticle composite system to elucidate the impact of nanoparticles on the degradation of polymer-nanoparticle composites. In order to have an in-depth understanding of the mechanisms of hydrolysis in PLA-nanoparticle composites, degradation processes were monitored by several surface sensitive techniques, including scanning electron microscopy, contact angle goniometry, atomic force microscopy, and sum frequency generation spectroscopy. As a second-order nonlinear optical technique, SFG spectroscopy was introduced to directly probe in situ chemical nature at the PLA-magnetic nanoparticle composite/aqueous interface, which allowed for the delineation of molecular mechanisms of various hydrolysis processes for degradation at the molecular level. The best PLA-NP material, with a concentration of 20% MNP in the composite, was found to enhance the drug release rate greater than 200 times while maintaining excellent controlled drug release characteristics. It was also found that during hydrolysis, various crystalline-like PLA domains on the surfaces of PLA-nanoparticle composites influenced various hydrolysis behaviors of PLA. Results from this study provide new insight into the design of nanomaterials with controlled degradation and drug release properties, and the underlined molecular mechanisms. The methodology developed in this study to characterize the polymer-nanoparticle composites is general and widely applicable.

Engineered iron oxide magnetic nanoparticles (MNPs) are one of the most promising tools in nanomedicine-based diagnostics and therapy. However, increasing evidence suggests that their specific delivery efficiency and potential long-term cytotoxicity remain a great concern. In this study, using 12 nm γ-Fe2O3 MNPs, we investigated three types of uptake pathways for MNPs into HepG2 cells: (1) a conventional incubation endocytic pathway; (2) MNPs co-administrated with microbubbles under ultrasound exposure; and (3) ultrasound delivery of MNPs covalently coated on the surface of microbubbles. The delivery efficiency and intracellular distribution of MNPs were evaluated, and the cytotoxicity induced by reactive oxygen species (ROS) was studied in detail. The results show that MNPs can be delivered into the lysosomes via classical incubation endocytic internalization; however, microbubbles and ultrasound allow the MNPs to pass through the cell membrane and enter the cytosol via a non-internalizing uptake route much more evenly and efficiently. Further, these different delivery routes result in different ROS levels and antioxidant capacities, as well as intracellular glutathione peroxidase activity for HepG2 cells. Our data indicate that the microbubble-ultrasound treatment method can serve as an efficient cytosolic delivery strategy to minimize long-term cytotoxicity of MNPs.

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