NIR-IIb-triggered photodynamic therapy combined with chemotherapy platform based on rare-earth-doped nanoparticles

Photodynamic therapy (PDT), with high spatiotemporal selectivity, minimal side effects and less drug resistance, has emerged as a promising approach for the treatment of cancer. However, inadequate penetration depth and poor efficacy seriously restrict its practical application. To address these challenges, we developed a combined therapy platform (RENP@C/D-FA) based on rare-earth-doped nanoparticles (RENPs) with a structure of NaErF₄:Tm(0.5%)@NaYF₄, on which photosensitizer Ce6 (chlorin e6) and chemo-therapeutic drug (DOX) (doxorubicin) were loaded by encapsulating with an amphiphilic polymer distearoyl phosphatidylethanolamine-polyethylene glycol-folic acid (DSPE-PEG-FA). RENPs with NaErF₄ as the matrix possess multiple excitation/emission peaks, enabling activation of PDT under near-infrared-IIb (NIR-IIb, 1500–1700 nm) excitation and luminescence imaging in NIR-IIb region by absorbing 808 nm near-infrared photons. Furthermore, DOX can be selectively released in the acidic microenvironment of tumors. Benefiting from the tumor targeting capability of folic acid, this platform can successfully ablate tumor cells and inhibit tumor growth by combining PDT and chemotherapy. This innovative approach holds great promise as a powerful tool for cancer treatment, showing the potential to revolutionize PDT.