A Review on the Structure-Response-Efficacy Optimization of Ultrasound-Responsive Micro/Nanobubbles for Cancer Therapy.

Ultrasound-responsive micro/nanobubbles (MNBs) are promising tools for targeted cancer therapy due to their controllable acoustic activation and real-time imaging. Despite extensive research, the quantitative relationship between bubble structure, acoustic response, and therapeutic efficacy remains poorly understood. This knowledge gap hinders parametric design and clinical standardization. This review summarizes recent advances from an engineering perspective, highlighting how structural parameters-such as size, shell, gas core, and ligand density-affect acoustic sensitivity and drug release. Furthermore, the roles of microfluidic electroporation and cell membrane coating are discussed in terms of controllable fabrication and preservation of biological functions, highlighting their significance for reproducible and predictable therapies. In conclusion, this review establishes a "Structure-Response-Efficacy (S-R-E)" framework to summarize the core relationships between structural design and acoustic modulation. We propose an engineering strategy based on a standardized parameter system to guide the predictable design and clinical translation of ultrasound-based theranostic platforms.