Xiaoju Zou

X-ray-induced nanoparticle-based photodynamic therapy of cancer

AIM In this study, Ce(3+)-doped lanthanum(III) fluoride (LaF3:Ce(3+)) nanoparticles were synthesized by a wet-chemistry method in dimethyl sulfoxide (DMSO) and their application as an intracellular light source for photodynamic activation was demonstrated. MATERIALS & METHODS The LaF3:Ce(3+)/DMSO nanoparticles have a strong green emission with a peak at approximately 520 nm, which is effectively overlapped with the absorption of protoporphyrin IX (PPIX). The nanoparticles were encapsulated into poly(D,L-lactide-co-glycolide (PLGA) microspheres along with PPIX. Upon irradiation with x-rays (90 kV), energy transfer from the LaF3:Ce(3+)/DMSO nanoparticles to PPIX occurs and singlet oxygen is generated for cancer cell damage. RESULTS The LaF3:Ce(3+)/DMSO/PLGA or LaF3:Ce(3+)/DMSO/PPIX/PLGA microspheres alone caused only sublethal cytotoxicity to the cancer cells. Upon x-ray irradiation, the LaF3:Ce(3+)/DMSO/PPIX/PLGA microspheres induced oxidative stress, mitochondrial damage and DNA fragmentation on prostate cancer cells (PC3). DISCUSSION The results indicate that x-rays can activate LaF3:Ce(3+) and PPIX nanocomposites, which can be a novel method for cancer destruction.

X-ray excited ZnS:Cu,Co afterglow nanoparticles for photodynamic activation

Copper and cobalt co-doped ZnS (ZnS:Cu,Co) afterglow nanoparticles were conjugated to photosensitizer tetrabromorhodamine-123 (TBrRh123) and efficient energy transfer from the nanoparticles to TBrRh123 was observed. In addition to their X-ray excited luminescence, the ZnS:Cu,Co nanoparticles also show long lasting afterglow, which continuously serve as a light source for photodynamic therapy (PDT) activation. Compared to TBrRh123 or ZnS:Cu,Co alone, the ZnS:Cu,Co-TBrRh123 conjugates show low dark toxicity but high X-ray induced toxicity to human prostate cancer cells. The results indicate that the ZnS:Cu,Co afterglow nanoparticles have a good potential for PDT activation.

Enhancement of protoporphyrin IX performance in aqueous solutions for photodynamic therapy

Molecular modification of protoporphyrin IX (PpIX) was conducted to improve its water solubility and therapeutic performance for photodynamic therapy. The carboxylic acid and the two nitrogen atoms in the core of PpIX molecule were protonated following by conjugation with 3-aminopropyl triethoxysilane (APTES). Then, folic acid (FA) was conjugated to the APTES-coated PpIX (MPpIX) through chemical bonding between FA and protonated PpIX. The results showed that APTES coating can stabilize PpIX and increase its water solubility. Consequently, this leads to the enhancement in luminescence and singlet oxygen production. Upon X-ray irradiation, singlet oxygen can be detected in the MPpIX but not in PpIX. This means that MPpIX can be used for deep cancer treatment as X-ray can penetrate deeply into tissue. Molecular modification also reduces the dark toxicity of PPIX and increases their cell uptake. All these traits indicate that the Molecular modification of PpIX may potentially improve the efficacy of photodynamic therapy for cancer treatment.

Enhancement of biophoton emission of prostate cancer cells by Ag nanoparticles

Ultraweak intrinsic bioluminescence of cancer cell is a noninvasive method of assessing bioenergetic status of the investigated cells. This weak biophoton emission generated by prostate cancer cells (PC3) was measured in the presence of Ag nanoparticles and its correlation with singlet oxygen production was investigated. The comparison between nanoparticles concentration, bioluminescence intensity, and cell survival showed that Ag nanoparticles do not significantly affect cell survival at used concentration but they increase cell bioluminescent processes. It was also confirmed that singlet oxygen contributes to biophoton emission, that Ag nanoparticles increase this contribution, and that there are secondary mechanisms independent of singlet oxygen by which Ag nanoparticles contribute to increased cellular bioluminescence, possibly through plasmon resonance enhancement of intrinsic fluorescence.

Synthesis of ZnS:Ag,Co water-soluble blue afterglow nanoparticles and application in photodynamic activation

Silver and cobalt co-doped ZnS (ZnS:Ag,Co) water-soluble afterglow nanoparticles were synthesized using a wet chemistry method followed by aging at room temperature. The nanoparticles had a cubic zinc blende structure with average sizes of approximately 4 nm and emitted a blue fluorescence emission centered at 441 nm due to radiative transitions from surface defects to Ag(+) luminescent centers. Intense afterglow emission peaking at 475 nm from the obtained nanoparticles was observed and was red-shifted compared to the fluorescence emission peak. X-ray photoelectron spectroscopy revealed a large increase of O/S ratio, indicating a surface oxidation process during aging. The S vacancies produced accordingly may contribute to form more electron traps and enhance afterglow. The ZnS:Ag,Co afterglow nanoparticles have a very low dark-toxicity and are applied as a light source for photodynamic therapy activation by conjugating with protoporphyrin together. Our preliminary study has shown that the ZnS:Ag,Co afterglow nanoparticles can significantly reduce the x-ray dosage used in activation and thus may be a very promising candidate for future x-ray excited photodynamic therapy in deep cancer treatment.