Hierarchical Nanostructures Enhance Ultrasound and Drug Delivery

By Dr. Chinta SidharthanReviewed by Laura ThomsonDec 23 2024

Acoustic manipulation uses sound waves to control microscopic objects in fluids and offers a non-invasive, precise, and biocompatible approach for biomedical applications. However, most studies have focused on static fluid environments, which has limited the relevance of acoustic manipulation in dynamic systems such as blood flow.

A recent study published in Advanced Materials introduced flower-like hierarchical nanostructures (HNS) assembled into microparticles (MPs) as innovative tools for acoustic manipulation in high-velocity fluid flows. The researchers showed that these HNS-MPs demonstrate exceptional biocompatibility and offer versatile material options with high surface area, enabling diverse applications, including real-time imaging, drug delivery, and water purification. These findings expand the potential of acoustic manipulation in biomedical and environmental sciences.

Background

The ability to control micro- and nanoparticles in fluid environments is essential for medical imaging, targeted drug delivery, and environmental purification. Acoustic manipulation, which uses ultrasound to trap and maneuver particles, has emerged as a promising technique due to its non-invasive nature and deep tissue penetration.

Current methods of acoustic manipulation often rely on gas-filled microbubbles, but these present challenges, such as limited stability, complex operational requirements, and restricted material design flexibility, in fast-flowing environments. Moreover, existing methods have generally been confined to static fluid conditions, which fail to address the complexities of dynamic fluid systems such as blood flow.

Living organisms and engineered materials with hierarchical structures have demonstrated remarkable abilities to interact with mechanical forces. However, despite extensive research on HNS for energy storage and catalysis, their potential for dynamic acoustic trapping remains underexplored.

About the study

The present study explored the design, synthesis, and application of flower-like hierarchical nanostructure microparticles (HNS-MPs) for acoustic trapping in dynamic fluid systems. Five types of HNS-MPs were synthesized using hydrothermal processes to create nanosheets that self-assembled into complex, flower-like architectures. The materials included zinc oxide (ZnO), bismuth oxyiodide (BiOI), polyimide (PI), titanium dioxide (TiO₂), and nickel metal-organic frameworks (Ni-MOF). These particles were characterized by their size and morphology, with diameters ranging from 1.1 to 4.9 micrometers.

Acoustic trapping experiments were conducted using focused ultrasound transducers in water-filled tubes of varying diameters and microfluidic channels. The transducers generated acoustic streaming forces that brought HNS-MPs into stable traps at flow velocities that simulated the conditions in veins and small arterioles. Comparative tests with conventional solid microparticles and gas-filled microbubbles were also conducted.

The simulations were performed to analyze the acoustic forces acting on the HNS-MPs. The study further validated the trapping performance of HNS-MPs in water and porcine blood, to explore their potential for in vivo applications.

Additional modifications were also performed, such as coating HNS-MPs with functional nanoparticles, which could enable their use as multimodal imaging contrast agents for ultrasound, optoacoustic, and magnetic resonance imaging. The researchers also conducted cytotoxicity and hemocompatibility tests using murine models and blood samples to confirm the biocompatibility of the coated HNS-MPs.

Major findings

The study found that HNS-MPs effectively enabled acoustic trapping in dynamic fluid flows. Compared to conventional solid microparticles and gas-filled bubbles, HNS-MPs maintained stable traps at flow velocities similar to venous and arteriolar blood flow. Furthermore, the performance was consistent across various materials, including BiOI, ZnO, TiO₂, PI, and Ni-MOF.

The experimental observations demonstrated that HNS-MPs formed traps even in established flows. The nanosheet-assembled structure of HNS-MPs was found to be crucial, as their sharp tips generated secondary acoustic streaming vortices, which enhanced particle aggregation.

Furthermore, the cytotoxicity tests indicated that most HNS-MPs exhibited high biocompatibility, with certain formulations enhancing cell growth. Hemocompatibility assessments also revealed no significant adverse effects, such as thrombogenicity or hemolysis, at concentrations used in acoustic trapping experiments.

Moreover, functionalization with nanoparticles, such as gold or indocyanine green, demonstrated the application of HNS-MPs as contrast agents in ultrasound, optoacoustic, and magnetic resonance imaging. These modifications maintained the trapping efficiency of HNS-MPs while enhancing their imaging properties.

The study also demonstrated the versatility of HNS-MPs as microrobots. The particles enabled photocatalytic dye degradation and efficient drug delivery in microfluidic setups. Real-time in vivo experiments confirmed their ability to trap and maneuver within mouse blood vessels while enabling three-dimensional optoacoustic imaging. These findings highlighted the potential of HNS-MPs for biomedical applications, including targeted drug delivery and real-time imaging.

Conclusions

The results demonstrated the potential of HNS-MPs as acoustically manipulatable agents in dynamic fluid environments. Their exceptional trapping efficiency, biocompatibility, and versatility make them suitable for diverse biomedical applications, including real-time imaging, targeted drug delivery, and environmental purification.

By overcoming the limitations of conventional materials, HNS-MPs represent a significant advancement in acoustic manipulation in dynamic fluid systems and biomedical engineering, paving the way for innovative therapeutic and diagnostic solutions.