Sonosensitive Niosomes for Cancer Therapy: Design Principles, Current Evidence, and Future Directions

Background/Objectives: Niosomes—vesicles formed through the self-assembly of non-ionic surfactants and cholesterol—have attracted attention as versatile, cost-effective, and chemically stable nanocarriers for delivering both hydrophilic and lipophilic anticancer drugs. Engineering these vesicles to respond to ultrasound (sonosensitivity) offers spatial and temporal control over drug release, potentially raising therapeutic concentrations at tumour sites while limiting systemic toxicity. This review compiles current evidence on the design principles of sonosensitive niosomes and situates them within the broader landscape of ultrasound-responsive vesicular carriers. Methods: In this narrative review, supported by a documented database search, PubMed/MEDLINE, Scopus, and Web of Science were searched in October 2026 without date or language limits, and 290 unique records were screened to establish whether any ultrasound-responsive niosomal formulation had been evaluated in a cancer model; background literature was identified from reference lists and citation searching. Results: Across the retrieved literature, surfactant and sonosensitizer selection, formulation and characterisation methods, and the acoustic mechanisms—primarily cavitation and reactive oxygen species (ROS) generation—that drive ultrasound-induced cargo release are examined. None of the 290 screened records reported an ultrasound-responsive niosomal formulation evaluated in a cancer model, and only seven studies applied ultrasound to niosomes, all of which were outside oncology. Design principles are necessarily extrapolated from the mature literature on ultrasound-responsive liposomes, liposome–microbubble hybrids, and sonodynamic nanosensitizers. Persistent challenges in in vivo stability, targeting accuracy, and release-kinetics control, together with barriers to clinical translation such as scale-up, acoustic-parameter standardisation, and regulatory considerations, are highlighted. Conclusions: Sonosensitive niosomes are a promising but still-emerging platform. Their advancement depends less on further feasibility demonstrations than on formulation standardisation, targeted surface engineering, quantitative mapping of release to defined acoustic parameters, and rigorous in vivo validation, before integration with theranostic, multi-stimuli-responsive, immunotherapeutic, or gene-therapy strategies, which for niosomes remain prospective.