Photodynamic therapy (PDT), as an emerging clinically approved modality, has been used for treatment of various cancer diseases. Conventional PDT strategies are mainly focused on superficial lesions because the wavelength of illumination light of most clinically approved photosensitizers (PSs) is located in the UV/VIS range that possesses limited tissue penetration ability, leading to ineffective therapeutic response for deep-seated tumors. The combination of PDT and nanotechnology is becoming a promising approach to fight against deep tumors. Here, the rapid development of new PDT modalities based on various smartly designed nanocomposites integrating with conventionally used PSs for deep tumor treatments is introduced. Until now many types of multifunctional nanoparticles have been studied, and according to the source of excitation energy they can be classified into three major groups: near infrared (NIR) light excited nanomaterials, X-ray excited scintillating/afterglow nanoparticles, and internal light emission excited nanocarriers. The in vitro and in vivo applications of these newly developed PDT modalities are further summarized here, which highlights their potential use as promising nano-agents for deep tumor therapy.

Photodynamic therapy (PDT) for deep-seated tumor is largely impeded by the limited penetration depth of excitation light in tissue. X-ray is considered as an ideal energy source to activate photosensitizers (PSs) located deep within the body with the assistance of scintillating nanoparticles (ScNPs). However, the efficacy under this concept is not satisfying due to the low scintillating luminescence and weak energy transfer from ScNPs to PSs. Here, mesoporous LaF3:Tb ScNPs were successfully synthesized by a facile hydrothermal process to act as PS carriers and X-ray energy transducers, owing to their good ionizing radiation stopping power and high luminescence efficiency. The formation mechanism of porous structure was elucidated in detail with classical crystallization theory. After a systematic investigation, LaF3:Tb ScNPs with optimized scintillating luminescence were obtained for loading Rose Bengal (RB) to establish an efficient FRET system, owing to their excellent spectral match. The FRET efficiency between ScNPs and RB was calculated to be as high as 85%. Under irradiation, enhanced (1)O2 generation induced by LaF3:Tb-RB nanocomposites via FRET process was detected. This LaF3:Tb-RB FRET system shows great potential to be applied in X-ray stimulated PDT for deep-seated tumors in the future.

Multifunctional LaF3:Tb scintillating nanoparticles (ScNPs) coated with homogenous layers of silica and subsequently tethered with RB covalently were elaborated. The nanoconjugates with a high colloidal stability and biocompatibility could generate a reasonable amount of (1)O2 through efficient energy transfer upon external illumination, which enables them to be potentially applied in diagnosis and photodynamic therapy for deep seated tumour.