title: Cell-specific and pH-activatable rubyrin-loaded nanoparticles for highly selective near-infrared photodynamic therapy against cancer.
abstract: Spatiotemporal control of singlet oxygen ((1)O2) 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 NMe2Se4N2 was activated to produce (1)O2. The pH-controllable release of (1)O2 specially damaged the lysosomes and thus killed cancer cells in a lysosome-associated pathway. The introduction of selenium into the rubyrin core enhanced the (1)O2 generation efficiency due to the heavy atom effect, and the substitution of dimethylaminophenyl moiety at meso-position led to the pH-controllable activation of NMe2Se4N2. Under near-infrared (NIR) irradiation, NMe2Se4N2 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 (ΦΔ = 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-NMe2Se4N2 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.
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science and ‡State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China.
authors.forename: Jiangwei
authors.initials: J
authors.lastname: Tian
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Xu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shen
authors.forename: Huangxian
authors.initials: H
authors.lastname: Ju
authors.forename: Li
authors.initials: L
authors.lastname: Jia
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Yu
mesh_terms: D000818:Animals; D005260:Female; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared
chemical_list: D011166:Porphyrins; D017382:Reactive Oxygen Species; C526398:rubyrin