Cavitation-on-a-Chip Enabled Size-Specific Liposomal Drugs for Selective Pharmacokinetics and Pharmacodynamics.

The size of liposomal drugs has been demonstrated to strongly correlate with their pharmacokinetics and pharmacodynamics. While the microfluidic method successfully achieves the production of liposomes with well-controlled sizes across various buffer/lipid flow rate ratio (FRR) settings, any adjustments to the FRR inevitably influence the concentration, encapsulation efficiency (EE), and stability of liposomal drugs. Here we describe a controllable cavitation-on-a-chip (CCC) strategy that facilitates the precise regulation of liposomal drug size at any desired FRR. The CCC-enabled size-specific liposomes exhibited striking differences in uptake and biodistribution behaviors, thereby demonstrating distinct antitumor efficacy in both tumor-bearing animal and melanoma patient-derived organoid (PDO) models. Intriguingly, as the liposome size decreased to approximately 80 nm, the preferential accumulation of liposomal drugs in the liver transitioned to a predominant enrichment in the kidneys. These findings underscore the considerable potential of our CCC approach in influencing the pharmacokinetics and pharmacodynamics of liposomal nanomedicines.

Phase-Optimized Multi-Step Phase Acoustic Metasurfaces for Arbitrary Multifocal Beamforming.

Focused ultrasound featuring non-destructive and high sensitivity has attracted widespread attention in biomedical and industrial evaluation. However, most traditional focusing techniques focus on the design and improvement of single-point focusing, neglecting the need to carry more dimensions of multifocal beams. Here we propose an automatic multifocal beamforming method, which is implemented using a four-step phase metasurface. The metasurface composed of four-step phases improves the transmission efficiency of acoustic waves as a matching layer and enhances the focusing efficiency at the target focal position. The change in the number of focused beams does not affect the full width at half maximum (FWHM), revealing the flexibility of the arbitrary multifocal beamforming method. Phase-optimized hybrid lenses reduce the sidelobe amplitude, and excellent agreement is observed between the simulation and experiments for triple-focusing beamforming metasurface lenses. The particle trapping experiment further validates the profile of the triple-focusing beam. The proposed hybrid lens can achieve flexible focusing in three dimensions (3D) and arbitrary multipoint, which may have potential prospects for biomedical imaging, acoustic tweezers, and brain neural modulation.