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: Jiangwei Tian, Lin Ding, Hai-Jun Xu, Zhen Shen, Huangxian Ju, Li Jia, Lei Bao, Jun-Sheng Yu
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 135 Issue 50 Pg. 18850-8 (Dec 18 2013) ISSN: 1520-5126 [Electronic] United States
• PMID: 24294991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Porphyrins
• Reactive Oxygen Species
• rubyrin

Topics

• Animals
• Female
• HeLa Cells
• Humans
• Hydrogen-Ion Concentration
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microscopy, Confocal
• Nanoparticles
• Neoplasms, Experimental (drug therapy, metabolism)
• Photochemotherapy
• Porphyrins (chemistry)
• Reactive Oxygen Species (metabolism)
• Spectroscopy, Near-Infrared