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转铁蛋白靶向的氧化还原超支化聚(酰胺-胺)功能化氧化石墨烯用于鼻咽癌的化疗增敏联合基因治疗。

Transferrin-targeting redox hyperbranched poly(amido amine)-functionalized graphene oxide for sensitized chemotherapy combined with gene therapy to nasopharyngeal carcinoma.

机构信息

a Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences , Guangzhou , China.

b Department of Nephrology, Ningbo Yinzhou Second Hospital , Ningbo , China.

出版信息

Drug Deliv. 2019 Dec;26(1):744-755. doi: 10.1080/10717544.2019.1642421.

Abstract

A drug and gene co-delivery system with chemotherapeutic sensibilization was prepared and used for nasopharyngeal carcinoma therapy. For this purpose, the graphene oxide (GO) was conjugated with the redox hyperbranched poly(amido amine) (HPAA) and then the targeting molecule, transferrin (Tf), was also conjugated. The obtained Tf-HPAA-GO could co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid (pMMP-9) effectively and showed the targeting effect to HNE-1 cells. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency. Besides that, Tf-HPAA-GO/DOC also showed the chemotherapeutic sensibilization effect, the formulation containing HPAA segments showed much higher cytotoxicity than free DOC. Benefiting from the sensibilization effect and DOC/pMMP-9 co-delivery strategy, this Tf-HPAA-GO/DOC/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by and assays. This strategy provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization, and targeting into one single platform, which showed a promising application in cancer therapy.

摘要

一种具有化疗增敏作用的药物和基因共递药系统被制备并用于鼻咽癌治疗。为此,将氧化石墨烯(GO)与氧化还原超支化聚(酰胺-胺)(HPAA)连接,然后再连接靶向分子转铁蛋白(Tf)。所得的 Tf-HPAA-GO 可以有效地共递多西他赛(DOC)和 MMP-9 shRNA 质粒(pMMP-9),并表现出对 HNE-1 细胞的靶向作用。该共递药系统具有有效的药物和基因递药能力,表现出高细胞毒性和基因转染效率。此外,Tf-HPAA-GO/DOC 还表现出化疗增敏作用,含有 HPAA 片段的配方比游离的 DOC 表现出更高的细胞毒性。得益于增敏作用和 DOC/pMMP-9 共递药策略,Tf-HPAA-GO/DOC/pMMP-9 共递药系统在联合治疗 HNE-1 肿瘤方面表现出显著改善的疗效,这通过体内和体外实验得到了证实。该策略提供了一种易于递药的系统,将药物/基因共递药、化疗增敏和靶向作用结合在一个单一的平台上,在癌症治疗中具有广阔的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff6c/6711081/9d6eb4289929/IDRD_A_1642421_SCH0001_C.jpg

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