Ultra-pH-sensitive nanoplatform for precise tumor therapy

The emergence of precision cancer treatment has triggered a paradigm shift in the field of oncology, facilitating the implementation of more effective and personalized therapeutic approaches that enhance patient outcomes. The pH of the tumor microenvironment (TME) plays a pivotal role in both the initiation and progression of cancer, thus emerging as a promising focal point for precision cancer treatment. By specifically targeting the acidic conditions inherent to the tumor microenvironment, innovative therapeutic interventions have been proposed, exhibiting significant potential in augmenting treatment efficacy and ameliorating patient prognosis. The concept of ultra-pH-sensitive (UPS) nanoplatform was proposed several years ago, demonstrating exceptional pH sensitivity and an adjustable pH transition point. Subsequently, diverse UPS nanoplatforms have been actively explored for biomedical applications, enabling the loading of fluorophores, therapeutic drugs, and photosensitizers. This review aims to elucidate the design strategy and response mechanism of the UPS nanoplatform, with a specific emphasis on its applications in surgical therapy, immunotherapy, drug delivery, photodynamic therapy, and photothermal therapy. The potential and challenges of translating in the clinic on UPS nanoplatforms are finally explored. Thanks to its responsive and easily modifiable nature, the integration of multiple functional units within a UPS nanoplatform holds great promise for future advancements in tumor precision theranositcs.