Dual-imaging enabled cancer-targeting nanoparticles.
Dual-imaging enabled cancer-targeting nanoparticles.
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DOI：
10.1002/adhm.201100055
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发表时间：
2012-07
影响因子：
10
通讯作者：
Yang, Jian
中科院分区：
文献类型：
--
作者：
Wadajkar, Aniket S.;Kadapure, Tejaswi;Zhang, Yi;Cui, Weina;Nguyen, Kytai T.;Yang, Jian
癌症是一种常见诊断疾病，也是美国第二大死亡原因。磁共振成像 (MRI)、计算机断层扫描 (CT)、正电子发射断层扫描 (PET) 和光学成像等常用诊断方式作为独立系统，由于灵敏度低、空间分辨率低、造影剂毒性等个体限制，以及造影剂对癌症部位的非特异性靶向导致诊断不准确等，其结果好坏参半。 [1]双/多模式成像系统具有特定个体成像模式的优点，可以克服与独立系统相关的限制。 [2]例如，MRI 提供卓越的组织对比度、穿透深度和高空间分辨率，而荧光成像则提供极高的灵敏度。因此，结合 MRI 造影剂和荧光剂的双成像方式将能够在术前和术中早期诊断癌症，具有更高的准确性。为了提高诊断准确性并减少对正常健康细胞的显着副作用，需要对成像造影剂进行位点特异性靶向。 [3]尽管通过渗漏的肿瘤脉管系统被动递送纳米粒子取得了一些成功，但主动靶向策略将为癌症靶向增加更多特异性。 [4]细胞选择性纳米颗粒专门靶向并将有效负载递送至癌细胞，从而最大限度地减少由于将有效负载递送至健康细胞而在全身给药中观察到的副作用。癌症靶向纳米颗粒系统的开发研究主要集中在偶联抗体、肽或适体以主动将纳米颗粒转运至癌细胞。其他靶向策略包括磁性靶向，有助于在磁场下的目标位置处纳米颗粒的积累。 [5]在此，我们报告了基于可生物降解光致发光聚合物[6]的突破性发展和超顺磁性氧化铁（Fe 3O 4）纳米颗粒的使用，开发了双成像癌症靶向纳米颗粒（DICT-NP）。双成像纳米颗粒近年来引起了广泛关注。例子包括罗丹明/FITC标记的顺磁性纳米颗粒、[7] DiI/DiR染料负载的聚丙烯酸涂覆的氧化铁纳米颗粒、[8]量子点涂覆的氧化铁纳米颗粒、[9]和Cy5。 5-标记的 PEG/壳聚糖包被的氧化铁纳米颗粒。[10, 11] 然而，已知这些系统中使用的荧光标签要么有毒，要么表现出光漂白作用。此外，将显像剂掺入纳米颗粒中可能会导致颗粒尺寸增加、复杂性增加以及不良生物反应的风险更高。我们最近开发了水溶性和水不溶性可生物降解光致发光聚合物（分别为WBPLP和BPLP），它们不含光漂白有机染料和细胞毒性量子点。 [6]该聚合物的可降解性和优异的光致发光性能（例如高量子产率、抗光漂白性和近红外区域的可调发射）使它们独一无二。 BPLP 已表现出优异的生物相容性以及体外和体内生物成像的巨大潜力。 [6]随着 BPLP 的发展，我们还开发了一系列聚（N-异丙基丙烯酰胺）（PNIPAAm）涂层磁性纳米粒子（MNP），用于受控和靶向药物输送。[12, 13] 除了用作 MRI 造影剂外，MNP 还被用作载体，将治疗剂输送、招募和保留到特定疾病部位……
Cancer is a commonly diagnosed disease and the second leading cause of deaths in the US Common diagnostic modalities such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and optical imaging have mixed results as a stand-alone system due to individual limitations such as low sensitivity, low spatial resolution, toxicity of contrast agents, and inaccurate diagnosis due to non-specific targeting of contrast agents to the cancer site.[1] Dual-/multi-modal imaging systems bearing the advantages of specific individual imaging modalities may overcome the limitations associated with the stand-alone systems.[2] For instance, MRI provides exceptional tissue contrast, penetration depth, and high spatial resolution, whereas fluorescence imaging provides extremely high sensitivity. Therefore, a dual-imaging modality combining MRI contrast and fluorescent agents will be able to diagnose cancers in early stage pre-operatively and intra-operatively with better accuracy. To improve the diagnostic accuracy and reduce the significant side effects to normal healthy cells, site-specific targeting of imaging contrast agents is required.[3] Although passive delivery of nanoparticles through leaky tumor vasculature shows some success, active targeting strategies will add more specificity for cancer targeting.[4] Cell-selective nanoparticles specifically target and deliver the payloads to cancer cells, minimizing the side effects observed in systemic drug administration due to the delivery of payloads to healthy cells. Research on the development of cancer targeting nanoparticle systems has been focused mainly on conjugating antibodies, peptides, or aptamers for actively transporting nanoparticles to cancer cells. Other targeting strategies include magnetic targeting that aids in the nanoparticle accumulation at the targeted site under a magnetic field.[5] Herein, we report the development of dualimaging enabled cancer-targeting nanoparticles (DICT-NPs) based on the breakthrough development of biodegradable photoluminescent polymers [6] and the use of superparamagnetic iron oxide (Fe 3O 4) nanoparticles. Dual-imaging nanoparticles have gained significant attention in recent years. Examples include rhodamine/FITC-labeled paramagnetic nanoparticles,[7] DiI/DiR dye loaded-polyacrylic acid-coated iron oxide nanoparticles,[8] quantum dot-coated iron oxide nanoparticles,[9] and Cy5. 5-labeled PEG/chitosan-coated iron oxide nanoparticles.[10, 11] However, the fluorescent tags used in these systems are known to either be toxic or display photobleaching. Moreover, incorporating imaging agents in nanoparticles may result in increased particle sizes, added complexity, and higher risk of adverse biological reactions. We have recently developed water-soluble and water-insoluble biodegradable photoluminescent polymers (WBPLP and BPLP, respectively), which do not contain photobleaching organic dyes and cytotoxic quantum dots.[6] The degradability of the polymers and the superior photoluminescent properties such as high quantum yield, photobleaching resistance, and tunable emission up to near infrared area, makes them unique. BPLPs have demonstrated excellent biocompatibility and great potential for bioimaging both in vitro and in vivo.[6] Along with the development of BPLPs, we have also developed a series of poly (N-isopropylacrylamide)(PNIPAAm)-coated magnetic nanoparticles (MNPs) for controlled and targeted drug delivery.[12, 13] In addition to their use as contrast agents for MRI, MNPs have also been used as carriers to deliver, recruit, and retain therapeutic agents to specific disease sites …
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DOI：
10.3181/0808-mr-250
发表时间：
2009-02
期刊：
Experimental biology and medicine (Maywood, N.J.)
影响因子：
--
作者：
Blanco E;Kessinger CW;Sumer BD;Gao J
通讯作者：
Gao J
影响因子：
3.3
作者：
Pinkernelle, J;Teichgräber, U;Bruhn, H
通讯作者：
Bruhn, H
影响因子：
14
作者：
Pouponneau, Pierre;Leroux, Jean-Christophe;Martel, Sylvain
通讯作者：
Martel, Sylvain
影响因子：
10.8
作者：
Nam, Hae Yun;Kwon, Seok Min;Jeong, Seo Young
通讯作者：
Jeong, Seo Young
影响因子：
38.3
作者：
通讯作者：
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