Fitzpatrick Institute for Photonics, Duke University, Durham, North Carolina 27708, United States.
ACS Nano. 2011 Jun 28;5(6):4679-87. doi: 10.1021/nn200511m. Epub 2011 May 12.
We report development of a nanoparticle-based, X-ray-activated anticancer "nanodrug" composed of yttrium oxide (Y(2)O(3)) nanoscintillators, a fragment of the HIV-1 TAT peptide, and psoralen. In this formulation, X-ray radiation is absorbed by the Y(2)O(3) nanoscintillators, which then emit UVA light. Absorption of UVA photons by nanoparticle-tethered psoralen has the potential to cross-link adenine and thymine residues in DNA. UVA-induced cross-linking by free psoralen upon activation with UVA light has previously been shown to cause apoptosis in vitro and an immunogenic response in vivo. Studies using the PC-3 human prostate cancer cell line demonstrate that X-ray excitation of these psoralen-functionalized Y(2)O(3) nanoscintillators yields concentration-dependent reductions in cell number when compared to control cultures containing psoralen-free Y(2)O(3) nanoscintillators.
我们报告了一种基于纳米粒子的 X 射线激活抗癌“纳米药物”的开发，该药物由氧化钇（Y(2)O(3)）纳米闪烁体、HIV-1 TAT 肽的一个片段和补骨脂素组成。在这种配方中，X 射线被 Y(2)O(3)纳米闪烁体吸收，然后发射 UVA 光。纳米粒子连接的补骨脂素吸收 UVA 光子，有可能使 DNA 中的腺嘌呤和胸腺嘧啶残基交联。以前已经证明，UVA 光激活时，游离补骨脂素的 UVA 诱导交联会导致体外细胞凋亡和体内免疫反应。使用人前列腺癌细胞系 PC-3 的研究表明，与含有无补骨脂素 Y(2)O(3)纳米闪烁体的对照培养物相比，X 射线激发这些补骨脂素功能化的 Y(2)O(3)纳米闪烁体可导致细胞数量的浓度依赖性减少。
