1508272-40-9Relevant academic research and scientific papers
Cell-specific and pH-activatable rubyrin-loaded nanoparticles for highly selective near-infrared photodynamic therapy against cancer
Tian, Jiangwei,Ding, Lin,Xu, Hai-Jun,Shen, Zhen,Ju, Huangxian,Jia, Li,Bao, Lei,Yu, Jun-Sheng
, p. 18850 - 18858 (2014/01/06)
Spatiotemporal control of singlet oxygen (1O2) release is a major challenge for photodynamic therapy (PDT) against cancer with high therapeutic efficacy and minimum side effects. Here a selenium-rubyrin (NMe2Se4N2)-loaded nanoparticle functionalized with folate (FA) was designed and synthesized as an acidic pH-activatable targeted photosensitizer. The nanoparticles could specifically recognize cancer cells via the FA-FA receptor binding and were selectively taken up by cancer cells via receptor-mediated endocytosis to enter lysosomes, in which NMe 2Se4N2 was activated to produce 1O2. The pH-controllable release of 1O 2 specially damaged the lysosomes and thus killed cancer cells in a lysosome-associated pathway. The introduction of selenium into the rubyrin core enhanced the 1O2 generation efficiency due to the heavy atom effect, and the substitution of dimethylaminophenyl moiety at meso-position led to the pH-controllable activation of NMe2Se4N 2. Under near-infrared (NIR) irradiation, NMe2Se 4N2 possessed high singlet oxygen quantum yield (ΦΔ) at an acidic pH (ΦΔ = 0.69 at pH 5.0 at 635 nm) and could be deactivated at physiological pH (Φ Δ = 0.06 at pH 7.4 at 635 nm). The subcellular location-confined pH-activatable photosensitization at NIR region and the cancer cell-targeting feature led to excellent capability to selectively kill cancer cells and prevent the damage to normal cells, which greatly lowered the side effects. Through intravenous injection of FA-NMe2Se4N 2 nanoparticles in tumor-bearing mice, tumor elimination was observed after NIR irradiation. This work presents a new paradigm for specific PDT against cancer and provides a new avenue for preparation of highly efficient photosensitizers.
