RESUMO
Two novel meso-A2B2-porphyrins (P1 and P2) with symmetrical phenylethynyl groups were synthesized by introducing amphiphilic triethylene glycol moieties onto the parent structure, which improved the near-infrared (NIR) absorbance and resulted in efficient singlet oxygen (1O2) generation. Through solvent-exchange based self-assembly approach, the corresponding hydrophilic nanoparticles (NPs) were fabricated. Thereby, as-prepared NP1 and NP2 presented obvious red-shifted absorbance in NIR region with homogeneous size, superb biocompatibility, higher 1O2 generation, and good phototoxicity as well as low dark cytotoxicity. Furthermore, cellular uptake behavior of the NPs was evaluated by confocal microscopy, which demonstrated that the NPs could easily go through the cell membrane and distribute in cytoplasm with desired fluorescence imaging performance. All results suggest the potential application of the two porphyrin-based NPs in fluorescence imaging guided cancer photodynamic therapy.
RESUMO
Porphyrin derivatives are the first-generation photosensitizers, and to design a strong near-infrared (NIR)-absorbing porphyrin with good water solubility is highly desired for better therapeutic effect to treat tumors. Herein, three new porphyrin derivatives, 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin (P1), 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) zinc porphyrin (ZnP1), and 5,15-bis(3,4-dimethoxyphenyl)-10,20-bis((4-methoxyphenyl)ethynyl) zinc porphyrin (ZnP2) have been synthesized. Among them, ZnP2 shows the longest and most intensive Q-bands in the near-infrared (NIR) region, as it endows the strongest light-harvesting capability and deepest tumor tissue penetration. The three porphyrin derivatives were prepared into nanoparticles (NPs) via nanoprecipitation method, and the NPs exhibit good water dispersibility and passive tumor-targeting property through enhanced permeability and retention effect. Furthermore, these NPs demonstrate both photodynamic and photothermal effects. Through a systematic study of the singlet oxygen quantum yield and cytotoxicity of P1, ZnP1, and ZnP2 NPs in vitro on Hela cells, it is found that ZnP2 shows the highest singlet oxygen quantum yield (79%), and its NPs show the best therapeutic efficacy in vitro. In vivo experiments disclosed that ZnP2 NPs present high phototoxicity, low dark toxicity, and excellent biocompatibility, and could be used as promising photothermogenic photosensitizer for cancer treatment.
Assuntos
Fármacos Fotossensibilizantes/química , Células HeLa , Humanos , Fotoquimioterapia , Porfirinas , ZincoRESUMO
Multifunctional theranostic platform coupling diagnostic and therapeutic functions holds great promise for personalized nanomedicine. Nevertheless, integrating consistently high performance in one single agent is still challenging. This work synthesized a sort of porphyrin derivatives (P) with high singlet oxygen generation ability and graphene quantum dots (GQDs) possessing good fluorescence properties. The P was conjugated to polyethylene glycol (PEG)ylated and aptamer-functionalized GQDs to gain a multifunctional theranostic agent (GQD-PEG-P). The resulting GQD-PEG-P displayed good physiological stability, excellent biocompatibility and low cytotoxicity. The intrinsic fluorescence of the GQDs could be used to discriminate cancer cells from somatic cells, whereas the large surface facilitated gene delivery for intracellular cancer-related microRNA (miRNA) detection. Importantly, it displayed a photothermal conversion efficiency of 28.58% and a high quantum yield of singlet oxygen generation up to 1.08, which enabled it to accomplish advanced photothermal therapy (PTT) and efficient photodynamic therapy (PDT) for cancer treatment. The combined PTT/PDT synergic therapy led to an outstanding therapeutic efficiency for cancer cell treatment.