The general mechanism of chemotherapeutic resistance is related to changes in the uptake and efflux rate of chemotherapeutic drugs or intracellular transport. In the progress of photodynamic and PTX combination therapy, the excessive use of photosensitizers (PSs) may cause side effects. Since PSs are exposed to light, they can still cause ongoing damage to normal cells. To effectively reduce this side effect, we propose a strategy to regulate the concentration of PTX in resistant cells using low concentrations of AIEgen PSs. In this work, the molecular structure of four AIEgen PSs ( TPEPy , TPECPy , TPAPy , and TPESPy ) were designed and synthesized featuring different “D−π−A” type structures. They displayed excellent optical properties , good biocompatibility , good PDT effect, mitochondrial targeting and cell imaging . Among these AIEgen PSs, TPESPy exhibited the strongest PDT effect in tumor cells and PTX resistant tumor cells. The reversal coefficient of PTX resistant tumor cells can be achieved as 2214. In addition, to demonstrate the transport mechanism of PTX within tumor cells, we further study the effect of uptake and expel PTX in the PTX resistant SKOV-3 cells. The results show the rate of uptake and expel PTX for PTX resistant SKOV-3 cells can be effectively changed by controlling the concentration of AIEgen PSs and light irradiation time, providing precise treatment options for drug-resistant tumor cells.
Aggregation-induced emission (AIE)-based photosensitizers (PSs) are well-known for their exceptional biocompatibility and high irradiation-induced reactive oxygen species (ROS) generation capacity, making them promising candidates for photodynamic therapy (PDT). In antitumor treatment, enhancing the spatiotemporal specificity of AIEgen PSs can maximize the efficacy of suppressing tumor cells. Lysosomes, as digestive cellular organelles, can be perturbed by various external stimuli, leading to cellular dysfunction and even apoptosis. This makes them ideal targets for effective and precise PDT. In this study, an AIE photosensitizer MEO-TTMN (MT) was encapsulated with a silica shell to develop AIE-based silica nanoparticles (NPs), MT@SiO2-MP NPs, for antitumor PDT. The absorption and emission peaks of these NPs were at 513 and 675 nm, respectively. Upon irradiation, MT@SiO2-MP NPs exhibited a stronger ROS generation capacity when compared with the commercial photosensitizer chlorin e6 (Ce6). The decoration of the morpholine group on the surface of the silica shell facilitated MT@SiO2-MP NPs to accumulate specifically in the cellular lysosomes. A high level of ROS was proven to be in situ generated at the lysosomal sites by irradiation, which led to the damage of lysosomes and subsequent apoptosis of tumor cells. The in vivo PDT of tumor-bearing mouse demonstrated that MT@SiO2-MP NPs significantly suppressed the growth of the tumor. This work has provided efficient lysosome-targeting NPs to improve PDT efficacy and accuracy, which is beneficial for cancer therapy in the field of nanomedicine research.
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