A recent study published in Engineering presents an innovative acoustofluidics-based approach for intracellular nanoparticle delivery. This method offers a new way to transport various functional nanomaterials into different cell types, potentially revolutionizing therapeutic applications and biophysical studies.

The efficient delivery of biomolecular cargos into cells is crucial for biomedical research, including gene therapies and drug delivery. However, traditional delivery methods such as endocytosis of nano-vectors, microinjection, and electroporation have limitations. They may require time-consuming processes, complex operations, or expensive equipment. Additionally, issues like low delivery efficiency and potential cell damage still exist.

The newly developed acoustofluidics-based method addresses these challenges. It uses standing acoustic waves generated in a glass capillary coated with cargo-encapsulated nanoparticles. By tuning the frequency of the acoustic waves, cells flowing through the capillary are pushed towards the capillary wall. This enables controllable contact between cells and nanoparticles, facilitating nanoparticle attachment to the cell membrane. The acoustic radiation force also increases membrane stress, which slightly deforms the cells and enhances membrane permeability, helping nanoparticles enter the cells.

In the study, researchers used two types of cargos, doxorubicin (DOX) and fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (FBSA), to test the method. They loaded these cargos into zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. The results showed that the method could successfully deliver nanoparticles loaded with different cargos into U937 and HeLa cells. The delivery efficiency was significantly enhanced compared to approaches without using acoustofluidics. What’s more, this method does not need bubbles or special acoustic contrast agents, which are often required in conventional sonoporation methods.

The researchers also investigated the properties of the cargo-encapsulated ZIF-8 nanoparticles and the impact of the delivery process on cell viability. They found that the nanoparticles had suitable characteristics for cargo encapsulation and release, and the acoustic waves and ZIF-8 decomposition had minimal effects on cell viability.

This acoustofluidics-based intracellular delivery approach provides a new option for achieving efficient and controllable intracellular delivery of biomolecular cargos. In the future, the research team plans to explore its application in delivering other types of cargo and in treating different cell types, including primary human cells. The findings of this study have the potential to contribute to the development of gene and cellular therapies, as well as fundamental research in cell mechanics.

The paper “Acoustofluidics-Based Intracellular Nanoparticle Delivery,” authored by Zhishang Li, Zhenhua Tian, Jason N. Belling, Joseph T. Rich, Haodong Zhu, Zhehan Ma, Hunter Bachman, Liang Shen, Yaosi Liang, Xiaolin Qi, Liv K. Heidenreich, Yao Gong, Shujie Yang, Wenfen Zhang, Peiran Zhang, Yingchun Fu, Yibin Ying, Steven J. Jonas, Yanbin Li, Paul S. Weiss, and Tony J. Huang. Full text of the open access paper: https://doi.org/10.1016/j.eng.2024.11.030. For more information about the Engineering, follow us on X (https://twitter.com/EngineeringJrnl) & like us on Facebook (https://www.facebook.com/EngineeringJrnl).