Tumor-responsive nanomedicine based on Ce3+-modulated up-/downconversion dual-mode emission for NIR-II imaging-guided dynamic therapy

Chemodynamic therapy (CDT) and photodynamic therapy (PDT) based on intratumoral generation of reactive oxygen species (ROS) have been playing crucial roles in conquering tumors. However, the above therapeutic methods are still constrained by the overexpressed tumor glutathione (GSH) and intrinsic tumor resistance to conventional organic photosensitizers. Herein, lanthanide-doped nanoparticles (LDNPs) were coated with inorganic bimetallic copper and manganese silicate nanospheres (CMSNs) and modified with sodium alginate (SA) for second near-infrared (NIR-II, 1000-1700 nm) imaging-guided CDT and PDT. Interestingly, cross-relaxation (CR) pathways between Ce3+ and Ho3+ and CR between Ce3+ and Er3+ are fully exploited to enable dual-mode upconversion (UC) and NIR-II downconversion (DC) emissions of LDNPs under 980 nm laser excitation. UC emission can induce CMSNs to produce toxic singlet oxygen (O-1(2)) for PDT, and the released Mn2+ and Cu+ ions caused by GSH-induced degradation of CMSNs can react with endogenous H2O2 to produce hydroxyl radical (OH) for CDT. Significantly, the ultrabright NIR-II DC emission endows the systems with exceptional optical imaging capabilities. All results affirm the potency of such an all in one theranostic nanomedicine integrating PDT, CDT and remarkable NIR-II imaging abilities accompanied by the function of modulating tumor microenvironment in cancer theranostics.

Automated summary

In this study, a multifunctional nanomedicine was developed for imaging-guided therapy. The nanomedicine showed exceptional optical imaging capabilities and enabled both photodynamic therapy and chemodynamic therapy.