Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles.
Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles.
复制标题
DOI：
10.1016/j.biomaterials.2011.04.078
复制
发表时间：
2011-09
期刊：
影响因子：
14
通讯作者：
Farokhzad, Omid C.
中科院分区：
文献类型：
--
作者：
Valencia, Pedro M.;Hanewich-Hollatz, Mikhail H.;Gao, Weiwei;Karim, Fawziya;Langer, Robert;Karnik, Rohit;Farokhzad, Omid C.
药物包裹的靶向纳米颗粒（NPs）的工程具有革命性的药物治疗的潜力。将靶向NP顺利转化到临床的主要挑战是开发用于预测和优化NP表面组成的方法，特别是当NP自组装过程中涉及不同化学性质的靶向配体（TL）时。在这里，我们研究了两种不同的有针对性的NP的自组装和特性，这两种NP被两种广泛使用的具有不同水溶性的TL修饰，并开发了表征和优化NP表面组成的方法。我们合成了两种不同的生物功能聚合物组成的聚（丙交酯-共-乙交酯）-b-聚乙二醇-RGD（PLGA-PEG-RGD，高水溶性TL）和PLGA-PEG-叶酸（低水溶性TL）。通过将TL缀合的聚合物与非缀合的PLGA-PEG以不同比例通过纳米沉淀混合来制备具有不同配体密度的靶向NP。对NP表面组成进行了定量，结果揭示了两种不同的纳米颗粒组装行为：对于PLGA-PEG-RGD的情况，发现几乎所有与聚合物缀合的RGD分子都在NP的表面上。相比之下，来自PLGA-PEG-叶酸盐的仅约20%的叶酸盐存在于NP表面上，而其余的可能由于PLGA和叶酸盐的疏水相互作用而仍然埋在PLGA NP核心中。最后，研究了NP的体外吞噬作用和细胞靶向作用，由此确定了表现出巨噬细胞最小摄取和靶向细胞最大摄取的NP制剂的窗口。这些结果强调了配体化学性质对自组装靶向纳米颗粒的靶向能力的影响，并提供了一种提高其靶向特异性的工程策略。
The engineering of drug-encapsulated targeted nanoparticles (NPs) has the potential to revolutionize drug therapy. A major challenge for the smooth translation of targeted NPs to the clinic has been developing methods for the prediction and optimization of the NP surface composition, especially when targeting ligands (TL) of different chemical properties are involved in the NP self-assembly process. Here we investigated the self-assembly and properties of two different targeted NPs decorated with two widely used TLs that have different water solubilities, and developed methods to characterize and optimize NP surface composition. We synthesized two different biofunctional polymers composed of poly(lactide-co-glycolide)-b-polyethyleneglycol-RGD (PLGA-PEG-RGD, high water solubility TL) and PLGA-PEG-Folate (low water solubility TL). Targeted NPs with different ligand densities were prepared by mixing TL-conjugated polymers with non-conjugated PLGA-PEG at different ratios through nanoprecipitation. The NP surface composition was quantified and the results revealed two distinct nanoparticle assembly behaviors: for the case of PLGA-PEG-RGD, nearly all RGD molecules conjugated to the polymer were found to be on the surface of the NPs. In contrast, only ~20% of the folate from PLGA-PEG-Folate was present on the NP surface while the rest remained presumably buried in the PLGA NP core due to hydrophobic interactions of PLGA and folate. Finally, in vitro phagocytosis and cell targeting of NPs was investigated, from which a window of NP formulations exhibiting minimum uptake by macrophages and maximum uptake by targeted cells was determined. These results underscore the impact the ligand chemical properties have on the targeting capabilities of self-assembled targeted nanoparticles and provide an engineering strategy for improving their targeting specificity.
登录
查看更多内容
影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
DOI：
10.2217/nnm.10.1
发表时间：
2010-02
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Mamo T;Moseman EA;Kolishetti N;Salvador-Morales C;Shi J;Kuritzkes DR;Langer R;von Andrian U;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
2.1
作者：
Gaillard, Claire;Duval, Monique;Bianco, Alberto
通讯作者：
Bianco, Alberto
影响因子：
10.8
作者：
Epstein-Barash, Hila;Gutman, Dikla;Golomb, Gershon
通讯作者：
Golomb, Gershon
影响因子：
38.3
作者：
Jiang, Wen;Kim, Betty Y. S.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.