ABSTRACT
The efficiency of photodynamic therapy (PDT) is severely constrained due to the innate hypoxic environment, besides the elevated level of glutathione (GSH). To get rid of the hypoxic environment and higher concentrations of GSH in the solid tumors, we propose an approach of oxygen self-sufficient multimodal imaging-guided nanocomposite CaO2-MnO2-UCNPs-Ce6/DOX (abbreviated as CaMn-NUC), in which CaO2 nanoparticles in the hydrophobic layer were seated on the hydrophilic MnO2 sheet and conjugated with chlorin e6 (Ce6) loaded upconversion nanoparticles (UCNPs-Ce6) via the click chemistry approach. CaMn-NUC was presented to overcome hypoxia and GSH-associated photodynamic resistance due to in situ oxygen generation and GSH reduction of MnO2 upon endocytosis, and a bulk amount of Mn2+ ions generated in the process under acidic tumor environment acts as the MRI contrast agent. Moreover, the MnO2 sheet protects Ce6 from self-degradation under irradiation; thus, it can be used to switch control of cellular imaging. Afterwards, in a regulated and targeted manner, the chemotherapeutic drug (doxorubicin hydrochloride, DOX) can be released with the degradation of CaMn-NUC in the acidic tumor microenvironment (TME). Thus, we testify a competent nanoplatform employing 808 nm-excited UCNPs-Ce6 for concurrent imaging and PDT in consideration of the large anti-Stokes shifts, deep penetration into biological tissues, narrow emission bands, and high spatial-temporal resolution of the UCNPs. Thus, our proposed nanoplatform postulates a strategy to efficiently kill cancer cells in a concentration- and time-dependent manner via the in situ oxygenation of solid tumor hypoxia to enhance the efficiency of multimodal imaging-guided chemo-photodynamic therapy.
