Abstract

Chemotherapy has been clinically used for cancer treatment. However, insufficient drug concentration at the target site limitsthe therapeutic effect. Here, we introduce an in vivo target drug enrichment method, which is based on spatiotemporal acousticnode modulation (STANM). In such a time-varying acoustic field, there are spatially-shifting acoustic radiation forces on the drug-loaded microparticles that move them toward the focus. Based on this mechanism, the enhanced enrichment by STANM showedan approximately 200-fold microparticle concentration increase compared with the control group of no acoustic enrichment. Thein vivo test in mice bladders verifies that the target drug enrichment based on STANM decreased tumor weight by 72.43% comparedto traditional chemotherapy. The proposed target drug enrichment method paves the way for enhanced cancer therapy.

FIGURE 1 Operation principle of in vivo target drug enrichment based on STANM. (a) The STANM system was used to enrich the drug-loadedmicroparticles to the tumor. Frequency shifting causes acoustic nodes moving toward the reflective surface in the acoustic field. Driven by ARF, drug-loaded microparticles are trapped by the acoustic nodes and move toward the tumor location as the position of the pressure nodes changes, achievingspatial enrichment of drugs at the tumor site. The arrows indicate microparticles motion. (b) Under STANM, drug-loaded microparticles are enrichedtargetedly at the tumor site, which increases the drug concentration and the drug penetration efficiency at the tumor location, as well as mediates tumorsuppression. (c) Ultrasound images are acquired in real time as drug-loaded microparticles are enriched in vivo under the STANM system. (d) Thetrapped microparticles move toward the target position in accordance with the variation of the pressure node positions. (e) Acoustofluidic effects onmicroparticles. Acoustic fields generate microparticle translation via ARF. The microparticles are uniformly distributed within the acoustic field. Whenthey are exposed to the acoustic field, the ARF induces microparticle motion and the final enrichment effect of microparticles under different acousticfields. Scale bar, 500 µm.

FIGURE 2 Enrichment performance of the STANM system in a bladder model. (a) Enrichment area of microparticles under different acousticfields (n = 5, means ± SD). (b) The iterative process of microparticles in the STANM system. (c) Microparticles enrichment area over time at differentoperating voltages. (d) Microparticles enrichment area over time at different frequencies. (e) Time varying curves of microparticles enrichment areawithin different shifting periods (n = 5, means ± SD).

https://doi.org/10.1002/adma.202517740