Impact of dendrimer surface functional groups on the release of doxorubicin from dendrimer carriers.
Impact of dendrimer surface functional groups on the release of doxorubicin from dendrimer carriers.
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DOI：
10.1021/jp411669k
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发表时间：
2014-02
期刊：
影响因子：
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通讯作者：
Mengen Zhang;Rui Guo;Mónika Kéri;I. Bányai;Yun Zheng;Mian Cao;Xueyan Cao;Xiangyang Shi
中科院分区：
文献类型：
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作者：
Mengen Zhang;Rui Guo;Mónika Kéri;I. Bányai;Yun Zheng;Mian Cao;Xueyan Cao;Xiangyang Shi
第五代(G5)聚酰胺胺树枝状大分子具有乙酰基(G5.NHAc)、缩水甘油羟基(G5.NGlyOH)和琥珀酸端基团(G5.SAH)，用于物理包裹抗癌药物阿霉素(DOX)。利用紫外可见光谱和一维、二维核磁共振等多种核磁共振技术，研究了不同树枝状大分子与DOX的相互作用。考察了G5树枝状大分子表面官能团对DOX包封率、释药动力学及对肿瘤细胞抑制作用的影响。我们发现三种类型的树枝状大分子都能够有效地包裹DOX并显示出对肿瘤细胞的治疗抑制作用，这仅与负载的DOX有关。核磁共振研究表明，G5.NHAc或G5.NGlyOH树枝状大分子与DOX的相互作用相对较强，这与G5.NHAc/DOX或G5.NGlyOH/DOX络合物中DOX的缓慢释放有很好的相关性。相反，G5.SAH和DOX之间的弱相互作用导致了DOX的快速释放，这表明G5.SAH/DOX复合体可能不是进一步体内研究的合适选择。我们的研究结果表明，树枝状大分子的表面官能团对于进一步设计基于树枝状大分子的多功能药物输送系统具有重要意义。
Generation 5 (G5) poly(amidoamine) dendrimers with acetyl (G5.NHAc), glycidol hydroxyl (G5.NGlyOH), and succinamic acid (G5.SAH) terminal groups were used to physically encapsulate an anticancer drug doxorubicin (DOX). Both UV-vis spectroscopy and multiple NMR techniques including one-dimensional NMR and two-dimensional NMR were applied to investigate the interactions between different dendrimers and DOX. The influence of the surface functional groups of G5 dendrimers on the DOX encapsulation, release kinetics, and cancer cell inhibition effect was investigated. We show that all three types of dendrimers are able to effectively encapsulate DOX and display therapeutic inhibition effect to cancer cells, which is solely associated with the loaded DOX. The relatively stronger interactions of G5.NHAc or G5.NGlyOH dendrimers with DOX than that of G5.SAH dendrimers with DOX demonstrated by NMR techniques correlate well with the slow release rate of DOX from G5.NHAc/DOX or G5.NGlyOH/DOX complexes. In contrast, the demonstrated weak interaction between G5.SAH and DOX causes a fast release of DOX, suggesting that the G5.SAH/DOX complex may not be a proper option for further in vivo research. Our findings suggest that the dendrimer surface functional groups are crucial for further design of multifunctional dendrimer-based drug delivery systems for various biomedical applications.