Fabrication of magnetic nanoparticles with controllable drug loading and release through a simple assembly approach.
Fabrication of magnetic nanoparticles with controllable drug loading and release through a simple assembly approach.
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通过简单的组装方法制造具有可控药物加载和释放的磁性纳米颗粒。
DOI：
10.1016/j.jconrel.2012.06.028
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发表时间：
2012-08-20
期刊：
影响因子：
--
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Fang C;Kievit FM;Veiseh O;Stephen ZR;Wang T;Lee D;Ellenbogen RG;Zhang M
基于纳米颗粒的癌症治疗有望提高药物输送的安全性和有效性。然而，制造具有高且可控的药物负载的一致的治疗诊断纳米颗粒仍然是一个挑战，主要是由于常规应用的繁琐的多步合成方法。在这里，我们提出了一种简单且高度可控的治疗诊断纳米颗粒组装方法，可以大大减少批次间的差异。该纳米颗粒系统的主要组分包括超顺磁性氧化铁纳米颗粒（SPION）、可生物降解且pH敏感的聚（β-氨基酯）（PBAE）共聚物、化疗剂阿霉素（DOX）。在这里，预先装载有药物的聚合物直接组装到SPION的表面，形成载药纳米颗粒（NP-DOX）。NP-DOX表现出679 μg DOX/mg铁的高载药效率，在细胞培养基中持续稳定长达7天，以及用于磁共振成像（MRI）的146 mM−1·s−1的强r2弛豫率。NP-DOX的药物释放分析显示DOX在pH 5.5和6.4（如在内体环境中）快速释放，在pH 7.4（生理条件）缓慢释放，证明了pH敏感的药物释放动力学。使用耐药C6神经胶质瘤细胞对NP-DOX功效的体外评价显示，与游离DOX相比，在治疗后24小时细胞内化增加300%，并且在治疗后72小时IC 50降低65%。这些纳米颗粒可以作为构建智能治疗诊断制剂的基础，用于通过MRI进行灵敏检测，并通过控制药物释放有效治疗癌症。
Nanoparticle-based cancer therapeutics promises to improve drug delivery safety and efficacy. However, fabrication of consistent theranostic nanoparticles with high and controllable drug loading remains a challenge, primarily due to the cumbersome, multi-step synthesis processes conventionally applied. Here, we present a simple and highly controllable method for assembly of theranostic nanoparticles, which may greatly reduce batch-to-batch variation. The major components of this nanoparticle system include a superparamagnetic iron oxide nanoparticle (SPION), a biodegradable and pH-sensitive poly (beta-amino ester) (PBAE) copolymer, a chemotherapeutic agent doxorubicin (DOX). Here the polymer pre-loaded with drug is directly assembled to the surface of SPIONs forming a drug loaded nanoparticle (NP-DOX). NP-DOX demonstrated a high drug loading efficiency of 679 µg DOX per mg iron, sustained stability in cell culture media up to 7 days, and a strong r2 relaxivity of 146 mM−1•s−1 for magnetic resonance imaging (MRI). The drug release analysis of NP-DOX showed fast DOX release at pH 5.5 and 6.4 (as in endosomal environment) and slow release at pH 7.4 (physiological condition), demonstrating pH-sensitive drug release kinetics. In vitro evaluation of NP-DOX efficacy using drug-resistant C6 glioma cells showed a 300% increase in cellular internalization at 24 h post-treatment and 65% reduction of IC50 at 72 h post-treatment when compared to free DOX. These nanoparticles could serve as a foundation for building smart theranostic formulations for sensitive detection through MRI and effective treatment of cancer by controlled drug release.
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DOI：
10.1038/nrc2607
发表时间：
2009-05
期刊：
Nature reviews. Cancer
影响因子：
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作者：
通讯作者：
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影响因子：
17.1
作者：
Kievit FM;Veiseh O;Fang C;Bhattarai N;Lee D;Ellenbogen RG;Zhang M
通讯作者：
Zhang M
影响因子：
13.3
作者：
Kohler, N;Sun, C;Zhang, MQ
通讯作者：
Zhang, MQ
影响因子：
41.2
作者：
通讯作者：
--
影响因子：
13.3
作者：
Fang, Chen;Bhattarai, Narayan;Sun, Conroy;Zhang, Miqin
通讯作者：
Zhang, Miqin