Quantum dot-folic acid conjugates as potential photosensitizers in photodynamic therapy of cancer
Quantum dot-folic acid conjugates as potential photosensitizers in photodynamic therapy of cancer
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DOI：
10.1039/c0pp00380h
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发表时间：
2011-05
影响因子：
3.1
通讯作者：
Vincent Morosini;T. Bastogne;C. Frochot;R. Schneider;A. François;F. Guillemin;M. Barberi-Heyob
中科院分区：
文献类型：
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作者：
Vincent Morosini;T. Bastogne;C. Frochot;R. Schneider;A. François;F. Guillemin;M. Barberi-Heyob
本研究探讨了生物共轭量子点（QD）作为光敏剂用于光动力治疗（PDT）的体外潜力。根据我们先前使用光敏剂的方法，叶酸似乎是将附着的治疗剂选择性递送至癌组织的最佳靶向配体。我们合成了亲水性近红外发射的CdTe（S）型量子点与叶酸共轭使用不同的间隔。在KB细胞上评价了与叶酸缀合或不与叶酸缀合的QD的光动力学效率，KB细胞由于其FR-α的过表达而充当阳性对照，并且HT-29细胞缺乏FR-α作为阴性对照。实验设计建议作为一个合理的解决方案，以评估每个实验因素（QD类型和浓度，光通量和激发波长，照射前的接触时间和细胞表型）的影响。我们证明，对于低于10 nM的浓度，QD在没有光暴露的情况下对两种细胞系几乎没有细胞毒性作用。而2.1 nM的QD显示出弱的光动力学活性，8 nM的浓度显著增强了光动力学效率，其特征在于光剂量依赖性响应。KB和HT-29细胞之间的光动力学效率的统计学显著差异在叶酸缀合的QD的情况下被证明。最佳条件导致增强的光细胞毒性反应，使我们能够验证量子点产生光动力学效应和叶酸缀合量子点的靶向PDT的能力。
This study examined the in vitro potential of bioconjugated quantum dots (QDs) as photosensitizers for photodynamic therapy (PDT). According to our previous approaches using photosensitizers, folic acid appears to be an optimal targeting ligand for selective delivery of attached therapeutic agents to cancer tissues. We synthesized hydrophilic near infrared emitting CdTe(S)-type QDs conjugated with folic acid using different spacers. Photodynamic efficiency of QDs conjugated or not with folic acid was evaluated on KB cells, acting as a positive control due to their overexpression of FR-α, and HT-29 cells lacking FR-α, as negative control. A design of experiments was suggested as a rational solution to evaluate the impacts of each experimental factor (QD type and concentration, light fluence and excitation wavelength, time of contact before irradiation and cell phenotype). We demonstrated that, for concentrations lower than 10 nM, QDs displayed practically no cytotoxic effect without light exposure for both cell lines. Whereas QDs at 2.1 nM displayed a weak photodynamic activity, a concentration of 8 nM significantly enhanced the photodynamic efficiency characterized by a light dose-dependent response. A statistically significant difference in photodynamic efficiency between KB and HT-29 cells was evidenced in the case of folic acid-conjugated QDs. Optimal conditions led to an enhanced photocytotoxicity response, allowing us to validate the ability of QDs to generate a photodynamic effect and of folic acid-conjugated QDs for targeted PDT.