Access to a novel near-infrared photodynamic therapy through the combined use of 5-aminolevulinic acid and lanthanide nanoparticles

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• 作者：Atsushi Shimoyama ; Hiroya Watase ; Yu Liu ; Shun-Ichiro Ogura ; Yuichiro Hagiya ; Kiwamu Takahashi ; Katsushi Inoue ; Tohru Tanaka ; Yasutoshi Murayama ; Eigo Otsuji ; Akihiro Ohkubo ; Hideya Yuasa
• 关键词：Photodynamic therapy ; Lanthanide nanoparticle ; 5-Aminolevulinic acid ; Up-conversion luminescence ; Near-infrared
• 刊名：Photodiagnosis and Photodynamic Therapy
• 出版年：December, 2013
• 年：2013
• 卷：10
• 期：4
• 页码：607-614
• 全文大小：1357 K

文摘

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Summary

Background

There have been considerable efforts to develop photodynamic therapy (PDT) for cancer, in which photoirradiation of a sensitizer delivered near cancer cells results in the conversion of oxygen into active species, causing cell destruction. Aiming at the best cancer selectivity, one PDT method employed protoporphyrin IX (PPIX), which selectively accumulated in cancer cells after oral administration of 5-aminolevulinic acid (ALA). The drawback, however, is that blue incident lights are required to excite PPIX, resulting in low tissue penetrability, and therefore limiting its application to surface cancers.

Methods

To overcome the low penetrability of the incident light, we employed a light energy upconverter, lanthanide nanoparticle (LNP), which, upon irradiation with highly penetrative near-infrared (NIR) radiation, emits visible light within the Q-band region of PPIX absorbance allowing its sensitization. To discover the optimum conditions for the LNP-assisted PDT, the cytotoxicity and PPIX-sensitizability of LNPs were first studied. Then, the LNP-assisted PDT was validated using the MKN45 cell line: cells were pretreated with ALA and LNP, irradiated with a 975-nm diode laser, and subjected to MTT assay to measure cell viability.

Results

The singlet oxygen generation on NIR-irradiation of the PPIX-LNP mixture was proved, indicating that the emission from LNP could excite the PPIX sensitizer. An intermittent NIR-irradiation for 32 min of MKN45, pretreated with LNP (1 mg/mL) and ALA (2 mM), caused 87% cell destruction.

Conclusions

The potential applicability of the NIR-irradiation PDT with ALA- and LNP-pretreated cancer cells was demonstrated.