ARTICLE
Porous Silicon Nanoparticle Photosensitizers for Singlet Oxygen and Their Phototoxicity against Cancer Cells Ling Xiao,† Luo Gu,‡ Stephen B. Howell,§ and Michael J. Sailor‡,* ‡
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States , †College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China, and §Department of Medicine and the Moores UCSD, Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, California 92093-0819, United States
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hotodynamic therapy (PDT) can be an effective clinical treatment for certain types of cancer because of its relatively low systemic toxicity and its noninvasive nature.1 The operational principle for PDT involves the conversion of groundstate molecular oxygen (3O2) to singlet oxygen (1O2) by energy transfer from a photoexcited molecule (a photosensitizer). The highly reactive 1O2 causes lethal damage to cancer cells and destruction of tumor vasculature.2,3 Despite the advantages of the therapy itself, photosensitizers in use today display toxic or other side effects that limit their use. For example, the first-generation photosensitizer Photofrin lacks a long wavelength absorption band and it exhibits prolonged residence time in the normal tissues of the body. If not protected from sunlight and other forms of bright light, the skin and eyes of the patient can become severely damaged. It takes only a few minutes of exposure to induce a light sensitivity response, and this sensitivity can persist for 412 weeks after administration of the therapeutic.4 More promising second-generation photosensitizers, such as Photosens, are based on a phthalocyanine motif with a strong long wavelength absorption band. However, most phthalocyanines and their relatives are hydrophobic, requiring delivery systems for clinical use,5,6 and patient photosensitivity remains a problem.7 Third-generation photosensitizers involve second-generation photosensitizers modified with targeting molecules for better tumor selectivity.8 Recent studies using nanoparticle hosts containing conventional organic photosensitizers have demonstrated improved water XIAO ET AL.
ABSTRACT Porous Si nanoparticles, prepared from electrochemically etched single crystal Si
wafers, function as photosensitizers to generate 1O2 in ethanol and in aqueous media. The preparation conditions for the porous Si nanoparticles were optimized to maximize (1) the yield of material; (2) its quantum yield of 1O2 production; and (3) its in vitro degradation properties. The optimal formulation was determined to consist of nanoparticles 146 ( 7 nm in diameter, with nominal pore sizes of 12 ( 4 nm. The quantum yield for 1O2 production is 0.10 ( 0.02 in ethanol and 0.17 ( 0.01 in H2O. HeLa or NIH-3T3 cells treated with 100 μg/mL porous Si nanoparticles and exposed to 60 J/cm2 white light (infrared filtered, 100 mW/cm2 for 10 min) exhibit ∼45% cell death, while controls containing no nanoparticles show 10% or 25% cell death, respectively. The dark control experiment yields
