Upconversion Nanoparticle Loaded with Chlorin e6 in a Lipid Shell for NIR Excitation-Based Photodynamic Cancer Therapy

Photodynamic therapy (PDT) is a clinically approved method for noninvasive cancer treatment with fewer side effects, high spatial resolution, low cost, and fast recovery time. However, the penetration depth of the excitation light has significantly restricted the advancement of PDT. Recently, upconverting nanoparticles have been suggested to extend the excitation spectrum of photosensitizers via luminescence resonance energy transfer (LRET). Herein, a photosensitizer, chlorin e6 (Ce6), with efficient generation of singlet oxygen (1O2), was combined with upconverting nanoparticles (UCNPs) to construct a near-infrared (NIR) light-activated UCNPs–Ce6 nanocomplex. The emission spectrum of the UCNPs was designed to align with the absorption spectrum of Ce6, enabling the formation of an LRET donor–acceptor pair. UCNPs–Ce6 demonstrated good biocompatibility, >50% LRET efficacy, and 1O2 generation under irradiation with an 808 or 980 nm laser. The photostability of Ce6 within the nanocomplex was significantly increased compared with free Ce6 molecules. Upon NIR light irradiation, UCNPs–Ce6 decreased the viability of DLD-1 and HCT116 cancer cells in a dose-dependent manner. The 808 nm laser was more suitable for nanocomplex-assisted PDT than the 980 nm laser due to relatively higher 1O2 production and fewer thermal side effects. In conclusion, the UCNPs–Ce6 nanocomplex is a promising NIR light-excitable PDT agent with great potential for deep-tissue photodynamic cancer therapy.