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Life sciences · Journal article
Nanomaterials · October 16, 2026
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Theranostic nanomedicines integrate therapeutic delivery with diagnostic imaging, but many conventional platforms primarily visualize nanocarrier localization and provide limited information on whether the therapeutic payload has been released, the intended treatment mechanism has been activated, or a meaningful biological response has occurred. Self-monitoring theranostic nanomedicines have emerged as functionally informative platforms capable of reporting their own biodistribution, biological fate, payload release, therapeutic activation, and downstream response in real time or through longitudinal imaging. This review summarizes the conceptual framework and design principles of self-monitoring nanomedicine, including always-on and activatable probes, Förster resonance energy transfer, self-quenching and dequenching mechanisms, ratiometric sensing, environment-responsive contrast agents, and multimodal imaging. Major imaging modalities, including fluorescence, magnetic resonance, photoacoustics, positron emission tomography, single-photon emission computed tomography, computed tomography, and ultrasound imaging, are discussed with emphasis on their respective capabilities and limitations for monitoring nanomedicine performance. Representative studies demonstrate the visualization of systemic biodistribution, target-site accumulation, carrier disassembly, drug and nucleic-acid release, photothermal and photodynamic activation, gene and RNA activity, oxidative stress, immune modulation, apoptosis, and pathogen clearance. Particular emphasis is placed on cancer theranostics, where self-monitoring nanomaterials can integrate tumor imaging with the assessment of intratumoral delivery, payload release, therapeutic activation, and early treatment response. Broader applications in inflammatory and immune-related diseases and infectious diseases further illustrate the general applicability of these monitoring principles beyond cancer. Despite substantial progress, clinical translation remains limited by ambiguous signal interpretation, insufficient quantitative validation, biological safety concerns, manufacturing complexity, and regulatory challenges. Future development should prioritize mechanistically defined and clinically actionable signals, orthogonal validation, standardized reporting, biodegradable and clearable materials, reproducible manufacturing, and compatibility with established imaging workflows. Self-monitoring theranostic nanomedicines may ultimately enable the transition from image-guided drug delivery to feedback-guided, adaptive, and personalized precision therapy.