Mesoporous cerium oxide-coated upconversion nanoparticles for tumor-responsive chemo-photodynamic therapy and bioimaging

Abstract

Long-term tumor hypoxia has always been a huge obstacle for oxygen dependent photodynamic therapy (PDT) and anticancer drug chemotherapy. Herein, a hollow-structured biophotocatalyst was developed by coating mesoporous cerium oxide (mCeO_x) on upconversion nanoparticles (UCNPs, NaGdF₄:Yb,Tm@NaGdF₄), and it can be initialized with a near-infrared (NIR) laser to achieve PDT with O₂ compensation by decomposing the endogenous H₂O₂ in the tumor microenvironment. A NIR laser with a long wavelength has low phototoxicity to biotissue, and the core–inert shell structured UCNPs can efficiently convert the NIR photons into ultraviolet (UV) light, which can further trigger CeO_x to produce reactive oxygen species (ROS). Moreover, the internal space of UCNPs@mCeO_x is ideal for storing chemotherapeutic doxorubicin (DOX), and adequate O₂ plays a key role in alleviating drug fastness via chemotherapy in hypoxic tumors, thereby strengthening the synergy between PDT and chemotherapy. After being injected into tumor-bearing mice intravenously, the nanomedicine was able to reach the tumor via an enhanced permeability and retention (EPR) effect. In addition, the capability to use the developed nanosystem in computed tomography (CT), magnetic resonance (MR) and upconversion luminescence (UCL) imaging was validated. Significantly, the NIR laser irradiated nanomedicine exhibits an excellent anticancer effect, implying promising theranostic applications.