Abstract
Rationale: Near-Infrared persistent luminescence (NIR-PL) nanomaterials that can continually emit low-energy photons after ceasing excitation has emerged as a new generation of theranostic nanoparticle drug delivery systems (NDDSs) for imaging-guided cancer therapy, which stems from their special ability to completely avoid tissue autofluorescence interference. However, unresponsive diagnostic capability, inefficient drug delivery, and poor biodegradability limit the efficacy of most reported NIR-PL-based NDDSs. Methods: Herein, a multifaceted tumor microenvironment (TME)-degradable theranostic drug delivery nanocapsule based on an ultrasmall persistent phosphor with a hollow mesoporous manganese-doped, DOX-loaded silica shell (Mn-ZGOCS-PEG) is developed to overcome the above drawbacks. Results: We demonstrate that the well-designed nanocapsule enables tumor-responsive controlled drug release with ameliorated therapeutic efficacy, TME-responsive autofluorescence interference-free NIR-PL tracing, and manganese-enhanced magnetic resonance (Mn-MR) monitoring for practical dual-modality image-guided antitumor treatment in vivo. Conclusion: Our results indicate that Mn-ZGOCS-PEG nanocapsules enable tumor-targeting augmented chemotherapy under the guidance of TME-responsive dual-MR/NIR-PL-modality imaging in vivo. We believe that our work provides a new paradigm for the development of smart NIR-PL-based NDDSs with ultrasensitive multimodal diagnostic capability, enhanced anticancer effect, and efficient biodegradability.