Redox-Sensitive Prodrug Molecules Meet Graphene Oxide: An Efficient Graphene Oxide-Based Nanovehicle toward Cancer Therapy
Redox-Sensitive Prodrug Molecules Meet Graphene Oxide: An Efficient Graphene Oxide-Based Nanovehicle toward Cancer Therapy
复制标题
氧化还原敏感的前药分子遇到氧化石墨烯：一种有效的基于氧化石墨烯的纳米载体用于癌症治疗
DOI：
10.1021/acsbiomaterials.9b00114
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发表时间：
2019
影响因子：
5.8
通讯作者：
Luan Yuxia
中科院分区：
文献类型：
--
作者：
Ma Naxin;Song Aixin;Li Zhonghao;Luan Yuxia
稳定性、缓释和不完全释药是氧化石墨烯纳米载体系统的关键问题。为了解决上述问题，我们利用氧化还原敏感的前药分子修饰氧化石墨烯(GO)构建了一种新的癌症治疗药物释放系统。通过氧化还原敏感的二硫键将抗癌药物阿霉素(DOX)与生物可降解、生物相容的两亲共聚物聚乙二醇PCL偶联，合成了抗癌药物聚乙二醇PCL-SS-DOX(前药)。通过Pcl-SS-DOX的疏水链段与GO的芳香环之间的疏水作用和π-π相互作用，制备了GO/前药纳米杂化材料。氧化还原敏感的PEG-PCL-SS-DOX分子将抗癌药物和分散剂/稳定剂结合在一起，形成GO。也就是说，前药分子在起分散剂/稳定剂作用的同时，还具有氧化还原敏感性，体外释药结果表明，它能保证抗癌药物在肿瘤部位有效释放。体外细胞毒性实验表明，GOPN能显著增加DOX在A549和B16细胞中的蓄积，有效地增强其抗癌活性。体内抗肿瘤和组织学检测结果表明，GOPN能降低DOX的全身毒性，对肿瘤生长有明显抑制作用。制备的GOPN可以解决以往报道的基于GO的药物释放系统的不完全和缓慢释放的问题，从而使DOX具有理想的抗癌作用。因此，目前构建的GOPN为有效的肿瘤治疗带来了新的机遇。
The stability and slow and incomplete drug release are the key problems for graphene oxide nanocarrier systems. To solve the above problems, we constructed a new drug delivery system from the graphene oxide (GO) decorated with the redox-sensitive prodrug molecules for cancer therapy. PEG-PCL-SS-DOX (prodrug) was synthesized by linking the anticancer drug doxorubicin (DOX) to the biodegradable and biocompatible amphiphilic copolymers PEG-PCL via redox-sensitive disulfide bond. The GO/prodrug nanohybrids (GOPN) was prepared via the hydrophobic and π–π interaction between the hydrophobic block of PCL-SS-DOX and the aromatic ring of GO. The redox-sensitive PEG-PCL-SS-DOX molecules integrate the anticancer drug and dispersant/stabilizing agent together into GO. In other words, prodrug molecules act as the dispersant/stabilizing agent and simultaneously provide the redox-sensitive property which ensures the effective release of the anticancer drug in tumor site demonstrated by the in vitro release results. The in vitro cell cytotoxicity showed that the GOPN could significantly enhance DOX accumulation in A549 and B16 cells and effectively enhance the anticancer activity. In vivo antitumor and histological examination results suggested that GOPN could reduce the DOX systemic toxicity with remarkable inhibition of tumor growth. The prepared GOPN could solve the incomplete and slow release problem of the previously reported GO-based drug delivery system, and resulting in the desirable anticancer effect of DOX. Therefore, the present constructed GOPN bring a new opportunity for effective cancer therapy.