Multi-shell structured nanocarriers with enhanced multiphoton upconversion luminescence efficiency for NIR-mediated targeted photodynamic therapy

Recently, upconversion nanoparticle (UCNP)-based photodynamic therapy (PDT) has attracted attention as an anticancer treatment that can address the limitations of light penetration depth to activate commercial photosensitizers (PSs) using the upconversion luminescence (UCL) process. However, the low UCL intensity of UCNPs and the overheating effect by the 980 nm NIR laser significantly reduced the therapeutic efficacy. To overcome these problems, it is essential to form UCNP with a multi-shell structure by varying the feed composition of Yb3+, which can improve the UCL intensity. To generate highly efficient theranostic systems, we prepared a multi-shell structured UCNP (UCNC60S3) system with enhanced UCL efficiency in this study that can activate two types of PSs with one laser irradiation and have tumor targeting properties. UCNC60S3 capable of emitting multiple wavelengths with enhanced photoluminescence efficiency (PL) were synthesized by a thermal decomposition method with two kinds of activators in a single nanoparticle. The UCNC60S3 with a multi-shell structure showed 267.6 and 387.3 fold enhancements in UCL efficiency than the core UCNP at wavelengths of 545 nm and 660 nm, respectively. In addition, multi-shell structured UCNPs combined with dual PS and tumor-targeted ligands (F-UCNC60S3-RC) exhibited a significant improvement in the therapeutic effect on cancer cells by near-infrared (NIR) irradiation. When an 808 nm laser at 2 W/cm2 intensity was irradiated for 5 min, F-UCNC60S3-RC showed 10 times higher phototoxicity to cancer cells than free PS. Therefore, the NIR-induced F-UCNC60S3-RC nanocarriers with a multi-shell structure and dual PS binding will be able to provide multiple emissions for bio-imaging as well as improved targeted cancer therapy.