Serial stimuli-responsive theranostic nanomaterials for cancer therapy and imaging

Traditional cancer drug therapies face major challenges, including high recurrence rates, systemic toxicity, and drug resistance. Serial stimuli-responsive (SSR) nanomaterials offer substantial advantages over single-stimulus systems for diagnosis and treatment by facilitating precise, adaptable, and effective drug delivery and triggering multiple disease site-specific on-demand responses tailored for personalized treatment of heterogeneous dynamic tumors under real-time monitoring. In this review, we highlight the transformative role of SSR nanomaterials with theranostic abilities. We explore SSR-associated innovative drug delivery systems based on smart nanomaterials, such as liposomes, dendrimers, polymeric nanoparticles, and micelles, which can be serially activated by endogenous stimuli, such as the pH and enzymes, or exogenous stimuli, such as heat, light, a magnetic field, and ultrasound. To our knowledge, this review is the first to discuss the design of smart nanomaterials for SSR multimodal cancer theranostics. We emphasize the emerging field of imaging-guided therapy, wherein theranostic agents facilitate the real-time monitoring of drug pharmacokinetics and therapeutic responses, allowing for the development of personalized treatment strategies targeting different tumor sites. Finally, we anticipate the role of SSR nanomaterials in transforming cancer-theranostic modalities for more effective and personalized therapies.