Yang Wensha, Read Paul W, Mi Jun, Baisden Joseph M, Reardon Kelli A, Larner James M, Helmke Brian P, Sheng Ke
Department of Radiation Oncology, University of Virginia, Charlottesville, VA, USA.
Int J Radiat Oncol Biol Phys. 2008 Nov 1;72(3):633-5. doi: 10.1016/j.ijrobp.2008.06.1916.
It has been proposed that quantum dots (QDs) can be used to excite conjugated photosensitizers and produce cytotoxic singlet oxygen. To study the potential of using such a conjugate synergistically with radiotherapy to enhance cell killing, we investigated the energy transfer from megavoltage (MV) X-rays to a photosensitizer using QDs as the mediator and quantitated the enhancement in cell killing.
The photon emission efficiency of QDs on excitation by 6-MV X-rays was measured using dose rates of 100-600 cGy/min. A QD-Photofrin conjugate was synthesized by formation of an amide bond. The role of Förster resonance energy transfer in the energy transferred to the Photofrin was determined by measuring the degree of quenching at different QD/Photofrin molar ratios. The enhancement of H460 human lung carcinoma cell killing by radiation in the presence of the conjugates was studied using a clonogenic survival assay.
The number of visible photons generated from QDs excited by 6-MV X-rays was linearly proportional to the radiation dose rate. The Förster resonance energy transfer efficiency approached 100% as the number of Photofrin molecules conjugated to the QDs increased. The combination of the conjugate with radiation resulted in significantly lower H460 cell survival in clonogenic assays compared with radiation alone.
The novel QD-Photofrin conjugate shows promise as a mediator for enhanced cell killing through a linear and highly efficient energy transfer from X-rays to Photofrin.
有人提出量子点(QDs)可用于激发共轭光敏剂并产生具有细胞毒性的单线态氧。为了研究将这种共轭物与放射疗法协同使用以增强细胞杀伤作用的潜力,我们研究了以量子点为介质时兆伏级(MV)X射线向光敏剂的能量转移,并对细胞杀伤增强情况进行了定量分析。
使用100 - 600 cGy/分钟的剂量率测量6 - MV X射线激发下量子点的光子发射效率。通过形成酰胺键合成了量子点 - 卟吩姆钠共轭物。通过测量不同量子点/卟吩姆钠摩尔比下的猝灭程度,确定了福斯特共振能量转移在转移至卟吩姆钠的能量中的作用。使用克隆形成存活试验研究了在共轭物存在下辐射对H460人肺癌细胞杀伤的增强作用。
6 - MV X射线激发的量子点产生的可见光子数量与辐射剂量率呈线性比例关系。随着与量子点共轭的卟吩姆钠分子数量增加,福斯特共振能量转移效率接近100%。在克隆形成试验中,与单独辐射相比,共轭物与辐射联合使用导致H460细胞存活率显著降低。
新型量子点 - 卟吩姆钠共轭物有望作为一种介质,通过从X射线到卟吩姆钠的线性且高效的能量转移来增强细胞杀伤作用。