Ultra-high FRET efficiency NaGdF4: Tb3+-Rose Bengal biocompatible nanocomposite for X-ray excited photodynamic therapy application
2018
Zhang, Wenli | Zhang, Xiaofeng | Shen, Yingli | Shi, Feng | Song, Chaojun | Liu, Tianshuai | Gao, Peng | Lan, Bin | Liu, Miao | Wang, Sicheng | Fan, Li | Lü, Hongbing
The limitation of light penetration depth invalidates the application of photodynamic therapy in deep-seated tumors. X-ray excited photodynamic therapy (X-PDT), which is based on X-rays excited luminescent nanoparticles (XLNP), provides a new strategy for PDT in deep tissues. However, the high X-ray dosage used and non-specific cytotoxicity of the nanoparticle-photosensitizer nanocomposite (NPs-PS) hamper in-vivo X-PDT applications. To address these problems, a simple and efficient NPs-PS nanocomposite using β-NaGdF4: Tb³⁺ nanoparticles and widely used PS called Rose Bengal (RB) was designed. With perfectly matched spectrum of NPs emission and RB absorption upon X-ray excitation and covalent conjugation of a large amount of RB on NP surfaces to minimize the energy transfer distance, the system demonstrated ultra-high FRET efficiency up to 99.739%, which leads to maximum production of singlet oxygen for PDT with significantly increased anti-tumor efficacy. By 2-aminoethylphosphonic acid surface modification of NPs, excellent biocompatibility was achieved even at a high concentration of 1 mg/mL. The in-vivo X-PDT efficacy was found around 90% of HepG2 tumor growth inhibition with X-ray dose of only 1.5 Gy, which shows the best anti-tumor efficacy at same X-ray dose level reported so far. The present work provides a promising platform for in-vivo X-PDT in deep tumors.
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