Semiconductor nanoparticles as energy mediators for photosensitizer-enhanced radiotherapy.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Yang
Wensha
W
Department of Radiation Oncology, University of Virginia, Charlottesville, VA, USA.
Read
Paul W
PW
Mi
Jun
J
Baisden
Joseph M
JM
Reardon
Kelli A
KA
Larner
James M
JM
Helmke
Brian P
BP
Sheng
Ke
K
D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D017323:Dihematoporphyrin Ether; D005290:Ferric Compounds; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms; D017785:Photons; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; D045663:Quantum Dots; D011789:Quantum Theory; D011878:Radiotherapy / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000379:methods*; D014965:X-Rays
D005290:Ferric Compounds; D017319:Photosensitizing Agents; C000499:ferric oxide; D011092:Polyethylene Glycols; D017323:Dihematoporphyrin Ether