Tianyi Chen, Junli Chen, Mingkai Chen, Ruixiao Song, Mingsi Wang, Xiaolong Yu
The maintenance of immune homeostasis is a cornerstone of health, and mastering its regulation is now the focus of groundbreaking disease treatments. This review innovatively proposes and elucidates the "Acoustic Immune Reprogramming" framework: using ultrasound as a catalyst and nanoplatforms as carriers to enable hierarchical, spatiotemporally precise immune microenvironment interventions. It represents an advanced form of immunomodulation distinguished by its capacity for physical programming-the proactive and rational remodeling of cellular functions and tissue microecology with spatiotemporal precision and dose control unavailable to molecular agents alone. The review covers key technological advances in acoustic-mediated biological barrier penetration, local microenvironment programming, and precise delivery of drugs/genes/antibodies. It highlights functional remodeling of macrophages, neutrophils, dendritic cells (DCs), and the synergistic network effect. From a systems engineering perspective, acoustic nanoplatforms offer remote physical modulation, non-invasive activation, spatiotemporal control, and integrate bioinformatics, materials science, medical engineering, and AI. Three challenges are identified: (1) deciphering "black box" mechanisms via acoustic immune biology and single-cell multi-omics; (2) calibrating biological acoustic dosimetry for "physical input-to-immune effect" translation, plus personalized treatment prediction via cavitation standardization/digital twinning; (3) managing safety boundaries for "immune-programmable" nanomaterials and intelligent closed-loop systems. This review establishes the acoustic immune reprogramming framework, providing a theoretical basis for immune modulation/precision medicine and guiding interdisciplinary breakthroughs. Future advances may make acoustic "spatiotemporal immune sculpting" a cornerstone of intelligent medicine.