Multifunctional nanoparticles integrated with imaging modalities (such as magnetic resonance and optical) and therapeutic drugs are promising candidates for future cancer diagnostics and therapy. While targeted drug delivery and imaging of tumor cells have been the major focus in engineering nanoparticle probes, no extensive efforts have been made towards developing sensing probes that can confirm and monitor intracellular drug release events. Here, we present quantum dot (Qdot)-iron oxide (IO) based multimodal/multifunctional nanocomposite probe that is optically and magnetically imageable, targetable and capable of reporting on intracellular drug release events. Specifically, the probe consists of a superparamagnetic iron oxide nanoparticle core (IONP) decorated with satellite CdS:Mn/ZnS Qdots where the Qdots themselves are further functionalized with STAT3 inhibitor (an anti-cancer agent), vitamin folate (as targeting motif) and m-polyethylene glycol (mPEG, a hydrophilic dispersing agent). The Qdot luminescence is quenched in this nanocomposite probe ("OFF" state) due to combined electron/energy transfer mediated quenching processes involving IONP, folate and STAT3 agents. Upon intracellular uptake, the probe is exposed to the cytosolic glutathione (GSH) containing environment resulting in restoration of the Qdot luminescence ("ON" state), which reports on uptake and drug release. Probe functionality was validated using fluorescence and MR measurements as well as in vitro studies using cancer cells that overexpress folate receptors.

译文

多功能纳米粒子与成像方式 (如磁共振和光学) 和治疗药物集成在一起,是未来癌症诊断和治疗的有希望的候选者。尽管肿瘤细胞的靶向药物递送和成像一直是工程纳米颗粒探针的主要重点,但尚未为开发可以确认和监测细胞内药物释放事件的传感探针做出广泛的努力。在这里,我们介绍了基于量子点 (Qdot)-氧化铁 (IO) 的多峰/多功能纳米复合探针,该探针可光学和磁性成像,可靶向并能够报告细胞内药物释放事件。具体来说,该探针由装饰有卫星CdS的超顺磁性氧化铁纳米颗粒核 (IONP) 组成: Mn/ZnS Qdots,其中Qdots本身被STAT3抑制剂 (一种抗癌剂),维生素叶酸 (作为靶向基序) 和m-聚乙二醇 (mPEG,一种亲水性分散剂)。由于涉及IONP,叶酸和STAT3试剂的结合的电子/能量转移介导的猝灭过程,Qdot发光在该纳米复合探针中被猝灭 (“关闭” 状态)。细胞内摄取后,探针暴露于含有胞质谷胱甘肽 (GSH) 的环境中,从而恢复了Qdot发光 (“ON” 状态),从而报告了摄取和药物释放。使用荧光和MR测量以及使用过表达叶酸受体的癌细胞的体外研究验证了探针的功能。

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