An activatable multimodal/multifunctional nanoprobe for direct imaging of intracellular drug delivery.
An activatable multimodal/multifunctional nanoprobe for direct imaging of intracellular drug delivery.
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DOI：
10.1016/j.biomaterials.2011.10.068
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发表时间：
2012-02
期刊：
影响因子：
14
通讯作者：
Santra, Swadeshmukul
中科院分区：
文献类型：
--
作者：
Mitra, Rajendra N.;Doshi, Mona;Zhang, Xiaolei;Tyus, Jessica C.;Bengtsson, Niclas;Fletcher, Steven;Page, Brent D. G.;Turkson, James;Gesquiere, Andre J.;Gunning, Patrick T.;Walter, Glenn A.;Santra, Swadeshmukul
与成像手段(如磁共振和光学)和治疗药物相结合的多功能纳米颗粒是未来癌症诊断和治疗的有前途的候选药物。虽然靶向药物输送和肿瘤细胞成像一直是工程纳米粒子探针的主要焦点，但还没有广泛的努力来开发能够确认和监测细胞内药物释放事件的传感探针。在这里，我们提出了基于量子点(QDot)-氧化铁(IO)的多模式/多功能纳米复合探针，它具有光学和磁性可成像、可靶向性和能够报告细胞内药物释放事件的特点。具体地说，该探针由一个装饰着卫星CDS的超顺磁性氧化铁纳米颗粒核心(IONP)组成：Mn/ZnS Qdots，其中Qdots本身进一步通过STAT3抑制剂(抗癌剂)、维生素叶酸(作为靶向基序)和m-聚乙二醇(m-PEG亲水分散剂)进行官能化。在这种纳米复合探针中，量子点的发光被猝灭，这是由于IONP、叶酸和STAT3试剂的电子/能量转移联合介导的猝灭过程。当细胞内摄取时，探针暴露在胞液中的谷胱甘肽(GSH)环境中，导致量子点发光恢复(“开”状态)，报告摄取和药物释放。通过荧光和磁共振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。
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 intra-cellular 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 intra-cellular 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 (m-PEG, 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.
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影响因子：
18.3
作者：
Mulder, Willem J. M.;Strijkers, Gustav J.;Van Tilborg, Geralda A. F.;Cormode, David P.;Fayad, Zahi A.;Nicolay, Klaas
通讯作者：
Nicolay, Klaas
影响因子：
5.7
作者：
McCann CM;Waterman P;Figueiredo JL;Aikawa E;Weissleder R;Chen JW
通讯作者：
Chen JW
影响因子：
9.8
作者：
Mulder, Willem J. M.;Strijkers, Gustav J.;Nicolay, Klaas;Griffioen, Arjan W.
通讯作者：
Griffioen, Arjan W.
影响因子：
16.6
作者：
Lee, Jae-Hyun;Lee, Kyuri;Cheon, Jinwoo
通讯作者：
Cheon, Jinwoo
DOI：
10.1073/pnas.0913679107
发表时间：
2010-05-04
影响因子：
11.1
作者：
John, Renu;Rezaeipoor, Robabeh;Boppart, Stephen A.
通讯作者：
Boppart, Stephen A.