Self-assembled phototheranostic nanomaterials used for photodynamic therapy (PDT) have attracted increasing attention owing to their several advantages. Herein, we developed a novel strategy for size-tunable self-assembled nanophotosensitizers for PDT through a simple method. A series of switchable self-assembled nanophotosensitizers (NanoPc90, NanoPc40, NanoPc20, and NanoPc10) of different particle sizes were readily prepared based on an amphiphilic silicon(IV) phthalocyanine (SiPc)-biotin con-jugate by regulating the amount of the Cremophor EL surfactant used. The photoactivities, including fluorescence and reactive oxygen species (ROS), of the self-assemblies could be regulated by the particle size. The self-assemblies could be specifically disassembled by tumor-overexpressing biotin receptors, leading to the recovery of quenched photoactivities. Demonstrated by the competitive assay, the self-assemblies were able to enter HepG2 cells through a biotin-receptor-mediated pathway, followed by biotin-receptor-triggered fluorescence recovery at the cellular level. Moreover, the particle size could also affect the in vitro and in vivo PDT effects and tumor targeting. The photocytotoxicity of NanoPc20 against HepG2 cells was more potent compared to that of NanoPc90 because of its strong intracellular fluorescence, higher intracellular ROS generation, and different subcellular localization. In addition, NanoPc20 showed higher in vivo tumor targeting and photodynamic therapeutic efficacy than NanoPc90. This work would provide a valuable reference for the development of self-assembled nanophotosensitizers for cancer diagnosis and therapy.
