Platinum on Nanodiamond: A Promising Prodrug Conjugated with Stealth Polyglycerol, Targeting Peptide and Acid‐Responsive Antitumor Drug
Platinum on Nanodiamond: A Promising Prodrug Conjugated with Stealth Polyglycerol, Targeting Peptide and Acid‐Responsive Antitumor Drug
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DOI：
10.1002/adfm.201304298
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发表时间：
2014-09
影响因子：
19
通讯作者：
Li Zhao;Yonghong Xu;Hongmei Qin;S. Abe;T. Akasaka;T. Chano;F. Watari;Takahide Kimura;N. Komatsu-N.-Koma
中科院分区：
文献类型：
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作者：
Li Zhao;Yonghong Xu;Hongmei Qin;S. Abe;T. Akasaka;T. Chano;F. Watari;Takahide Kimura;N. Komatsu-N.-Koma
在纳米医学领域，需要具有多种功能的纳米颗粒用于生物医学成像和药物输送等体内应用。因此，纳米粒子的化学功能化得到了广泛的研究。据报道，包覆聚甘油(PG)及其衍生物的纳米金刚石(ND)在生理环境中具有良好的溶解性，具有避免非特异性摄取的隐蔽性，具有被特定细胞摄取的靶向性，以及具有酸响应药物释放特性以杀死癌细胞。ND首先与PG接枝，得到的ND-PG在生理介质中具有很高的溶解性。由于PG中大量的羟基为进一步的表面功能化提供了支架，因此将靶向RGD多肽和铂基药物固定在一起，得到了ND-PG-RGD、ND-PG-铂和ND-PG-RGD-铂。具有本征荧光的ND也被PG和RGD功能化，以确定细胞摄取和细胞内荧光定位。细胞实验结果表明，PG涂层可保护HeLa和U87 MG细胞不摄取FND。相反，FND-PG-RGD被U87 MG细胞摄取，而不是HeLa细胞，表现出高的靶向效率。当应用ND-PG-RGD-PT时，U87 MG对HeLa具有选择性杀伤作用。多功能ND是一种很有前途的靶向化疗前药。
In the field of nanomedicine, nanoparticles with various functions are required for in vivo applications such as biomedical imaging and drug delivery. Therefore, chemical functionalization of nanoparticles has been extensively investigated. Herein, nanodiamond (ND) coated with polyglycerol (PG) and its derivatives is reported to impart good solubility in a physiological environment, a stealth nature to avoid nonspecific uptake, a targeting property to be taken up by a specific cell, and an acid‐responsive drug release property to kill cancer cells. ND is first grafted with PG and the resulting ND‐PG has a high solubility in physiological media. Since a large number of hydroxyl groups in PG provide scaffolds for further surface functionalization, the targeting RGD peptide and Pt‐based drug are immobilized to give ND‐PG‐RGD, ND‐PG‐Pt and ND‐PG‐RGD‐Pt. The ND with intrinsic fluorescence is also functionalized by PG and RGD to confirm cellular uptake and intracellular localization fluorescently. The results of the cell experiments indicate that PG coating shielded fND from the uptake by HeLa and U87MG cells. In contrast, fND‐PG‐RGD is taken up by U87MG, not HeLa cells, exhibiting high targeting efficacy. When ND‐PG‐RGD‐Pt is applied, U87MG is selectively killed against HeLa. The multi‐functional ND is a promising prodrug in targeting chemotherapy.