Advances in ultrasound-activated nano-sonosensitizers for cancer treatment: a systematic review and meta-analysis
Abstract
Ultrasound (US)-activated nanotherapies represent a transformative frontier in oncology, leveraging the noninvasive deep penetration of acoustic energy for targeted tumor destruction. However, this field lacks a quantitative synthesis to guide the rational design of sono-sensitizing nanoparticles (NPs) and the optimization of therapeutic protocols. To address this issue, we performed a systematic review and meta-analysis of 144 recent research reports, establishing an evidence-based design hierarchy for nano-sonosensitizers. A meta-analysis of 86 in vitro studies revealed a profound synergistic reduction in cell viability when NPs were activated by US (pooled standard mean difference, SMD = -13.16, 95% CI [-14.67, -11.64], p < 0.001). NP size was the most influential design factor. Particles smaller than 50 nm showing the greatest effect in vitro (SMD = -13.32) and strongest tumor reduction in vivo (SMD = 5), a finding consistent with optimal exploitation of the enhanced permeability and retention (EPR) effect for tumor accumulation. Specific roles of materials were identified: polymeric NPs excelled in drug delivery (SMD = -19.36 versus US alone), while inorganic NPs served as direct sonocatalysts. This work provides a definitive quantitative framework to advance US-activated nanotherapy from exploratory discovery to clinical precision. To realize this potential, we recommend the adoption of standardized acoustic dosimetry and material characterization and inclusion of…
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Evidence Hub reads this as a meta-analysis, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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