Induced clustered nanoconfinement of superparamagnetic iron oxide in biodegradable nanoparticles enhances transverse relaxivity for targeted theranostics.
Induced clustered nanoconfinement of superparamagnetic iron oxide in biodegradable nanoparticles enhances transverse relaxivity for targeted theranostics.
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DOI：
10.1002/mrm.24622
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发表时间：
2013-12
影响因子：
3.3
通讯作者：
Fahmy, Tarek M.
中科院分区：
文献类型：
--
作者：
Ragheb, Ragy R. T.;Kim, Dongin;Bandyopadhyay, Arunima;Chahboune, Halima;Bulutoglu, Beyza;Ezaldein, Harib;Criscione, Jason M.;Fahmy, Tarek M.
“治疗诊断学”结合了治疗和诊断剂，是无创成像和药物输送的新兴有价值工具。在这里，我们报告了一种结合了这两种功能的固体可生物降解多功能纳米颗粒。聚（丙交酯-乙交酯）纳米颗粒经过精心设计，可限制用于磁共振成像的超顺磁性氧化铁对比，同时能够控制药物输送并靶向特定细胞。为了实现这种双重模式，脂肪酸被用作表面配体和聚合物基质中封装的氧化铁的锚定物。我们证明，脂肪酸改性的氧化铁在药物降解释放过程中延长了造影剂在聚合物基质中的保留时间。抗体-脂肪酸表面修饰促进细胞靶向和随后的细胞内化，同时在颗粒配制过程中诱导封装的脂肪酸修饰的超顺磁性氧化铁聚集。这种诱导的簇限制导致纳米颗粒内聚集，因此与没有脂肪酸配体的纳米颗粒（160 mM−1 s−1）相比，具有更高的横向弛豫率r2（294 mM−1 s−1），并且比市售的超顺磁性氧化铁纳米颗粒（89 mM−1 s−1）更高。聚丙交酯乙交酯中超顺磁性氧化铁的聚集不会影响甲氨蝶呤或氯膦酸盐等封装药物的控制释放及其随后的药理活性，从而突出了我们系统的完整治疗诊断能力。
Combined therapeutic and diagnostic agents, “theranostics” are emerging valuable tools for noninvasive imaging and drug delivery. Here, we report on a solid biodegradable multifunctional nanoparticle that combines both features. Poly(lactide-co-glycolide) nanoparticles were engineered to confine superparamagnetic iron oxide contrast for magnetic resonance imaging while enabling controlled drug delivery and targeting to specific cells. To achieve this dual modality, fatty acids were used as anchors for surface ligands and for encapsulated iron oxide in the polymer matrix. We demonstrate that fatty acid modified iron oxide prolonged retention of the contrast agent in the polymer matrix during degradative release of drug. Antibody-fatty acid surface modification facilitated cellular targeting and subsequent internalization in cells while inducing clustering of encapsulated fatty-acid modified superparamagnetic iron oxide during particle formulation. This induced clustered confinement led to an aggregation within the nanoparticle and, hence, higher transverse relaxivity, r2, (294 mM−1 s−1) compared with nanoparticles without fatty-acid ligands (160 mM−1 s−1) and higher than commercially available superparamagnetic iron oxide nanoparticles (89 mM−1 s−1). Clustering of superparamagnetic iron oxide in poly(lactide-co-glycolide) did not affect the controlled release of encapsulated drugs such as methotrexate or clodronate and their subsequent pharmacological activity, thus highlighting the full theranostic capability of our system.
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影响因子：
10.8
作者：
Kester M;Heakal Y;Fox T;Sharma A;Robertson GP;Morgan TT;Altinoğlu EI;Tabaković A;Parette MR;Rouse SM;Ruiz-Velasco V;Adair JH
通讯作者：
Adair JH
影响因子：
10.8
作者：
Nasongkla, Norased;Bey, Erik;Gao, Jinming
通讯作者：
Gao, Jinming
影响因子：
15
作者：
Pan, Dipanjan;Caruthers, Shelton D.;Lanza, Gregory M.
通讯作者：
Lanza, Gregory M.
影响因子：
4.9
作者：
Guthi JS;Yang SG;Huang G;Li S;Khemtong C;Kessinger CW;Peyton M;Minna JD;Brown KC;Gao J
通讯作者：
Gao J
影响因子：
14
作者：
Lee, Eddy S. M.;Shuter, Borys;Wang, Shih-Chang
通讯作者：
Wang, Shih-Chang