Acoustofluidics, the integration of acoustics and microfluidics, is a rapidly growing research field that is addressing challenges in biology, medicine, chemistry, engineering, and physics. In particular, acoustofluidic separation of biological targets from complex fluids has proven to be a powerful tool due to the label-free, biocompatible, and contact-free nature of the technology. By carefully designing and tuning the applied acoustic field, cells and other bioparticles can be isolated with high yield, purity, and biocompatibility. Recent advances in acoustofluidics, such as the development of automated, point-of-care devices for isolating sub-micron bioparticles, address many of the limitations of conventional separation tools. More importantly, advances in the research lab are quickly being adopted to solve clinical problems. In this review article, we discuss working principles of acoustofluidic separation, compare different approaches of acoustofluidic separation, and provide a synopsis of how it is being applied in both traditional applications, such as blood component separation, cell washing, and fluorescence activated cell sorting, as well as emerging applications, including circulating tumor cell and exosome isolation.

Fibroblast activation protein-α (FAPα) is a tumor-associated antigen uniquely expressed by reactive stromal fibroblasts in the majority of human epithelial tumors. FAPα also possesses both post-prolyl peptidase and endopeptidase activities. Consequently, FAPα is increasingly considered as a potential pan-tumor target for designing tumor-targeted prodrugs. We previously conjugated Doxorubicin (Dox) with a FAPα-specific dipeptide (Z-Gly-Pro) to develop a FAPα-targeting prodrug of Dox (FTPD). The aim of current work was to validate the tumor targeting of this targeted-delivery strategy. The results demonstrated that FTPD could effectually release Dox upon the hydrolysis of FAPα as well as the incubation with tumor homogenate of FAPα-positive tumor (4T1 tumor), while it was highly stable in mouse plasma and a variety of tissue homogenates including heart, liver, and so on. And the FAPα-cleaved FTPD exhibited significantly higher cytotoxicity against 4T1 cells in vitro than the uncatalyzed prodrug. Additionally, FTPD produced similar antitumor efficacy in 4T1 tumor-bearing mice to free Dox without obvious cardiotoxic effect. Moreover, subsequent study indicated that the accumulation of FTPD reduced significantly in the heart compared to free Dox. These findings suggest that such FAPα-based prodrug strategy is promising to achieve targeted delivery of antitumor agents.

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