Near-Infrared-Triggered Photodynamic, Photothermal, and on Demand Chemotherapy by Multifunctional Upconversion Nanocomposite

In an attempt to integrate photodynamic therapy (PDT) with photothermal therapy and chemotherapy for enhanced anticancer activity, we have rationally synthesized a multifunctional upconversion nanoplatform using NaYF 4:Yb/Tm/Er/Fe nanoparticles (NPs) as the core and NaYbF 4:1% Tm as a shell. The as-synthesized core–shell upconversion (CSU) NPs exhibited diverse and enhanced photoluminescence emissions in a wide range (UV to NIR) consequent upon Fe 3+ doping in the core and fabrication of an active shell. Subsequently, CSU was first decorated with titania NPs as photosensitizers. Next, the mesoporous silica (MS) shell loaded with doxorubicin (DOX) via a photocleavable Ru complex as the gating molecule was developed around titania-containing CSU. Finally, gold nanorods (GNRs) with localized surface plasmon resonance (LSPR) at 800 nm were incorporated around the MS layer to obtain the multifunctional nanoplatform. We demonstrated that the UV, blue, and NIR emissions from the CSU produced ROS-mediated PDT through titania activation, induced DOX release through photocleavage of the Ru complex, and generated hyperthermia by LSPR activity of GNRs, respectively, upon a single NIR excitation through FRET. The therapeutic efficacy was validated on HeLa cell lines in vitro by various microscopic and biochemical studies under a significantly milder NIR irradiation and lower dosage of the nanoplatforms, which have been further demonstrated as diagnostic nanoprobes for cell imaging.