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聚合物功能化还原氧化石墨烯上超高共载姜黄素和紫杉醇用于高效协同抗癌治疗。

Exceedingly Higher co-loading of Curcumin and Paclitaxel onto Polymer-functionalized Reduced Graphene Oxide for Highly Potent Synergistic Anticancer Treatment.

机构信息

Centre for Nanotechnology and Advanced Materials (CENTAM), Faculty of Engineering, University of Nottingham Malaysia Campus (UNMC), Semenyih, Selangor 43500, Malaysia.

School of Biosciences, Faculty of Science, UNMC, Semenyih, Selangor 43500, Malaysia.

出版信息

Sci Rep. 2016 Sep 6;6:32808. doi: 10.1038/srep32808.

DOI:10.1038/srep32808
PMID:27597657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5011726/
Abstract

Metastasis of lung carcinoma to breast and vice versa accounts for one of the vast majority of cancer deaths. Synergistic treatments are proven to be the effective method to inhibit malignant cell proliferation. It is highly advantageous to use the minimum amount of a potent toxic drug, such as paclitaxel (Ptx) in ng/ml together with a natural and safe anticancer drug, curcumin (Cur) to reduce the systemic toxicity. However, both Cur and Ptx suffer from poor bioavailability. Herein, a drug delivery cargo was engineered by functionalizing reduced graphene oxide (G) with an amphiphilic polymer, PF-127 (P) by hydrophobic assembly. The drugs were loaded via pi-pi interactions, resulting in a nano-sized GP-Cur-Ptx of 140 nm. A remarkably high Cur loading of 678 wt.% was achieved, the highest thus far compared to any other Cur nanoformulations. Based on cell proliferation assay, GP-Cur-Ptx is a synergistic treatment (CI < 1) and is highly potent towards lung, A549 (IC50 = 13.24 μg/ml) and breast, MDA-MB-231 (IC50 = 1.450 μg/ml) cancer cells. These positive findings are further confirmed by increased reactive oxygen species, mitochondrial membrane potential depletion and cell apoptosis. The same dose treated on normal MRC-5 cells shows that the system is biocompatible and cancerous cell-specific.

摘要

肺癌和乳腺癌的转移占癌症死亡的绝大多数。协同治疗已被证明是抑制恶性细胞增殖的有效方法。以最小的有效毒性药物(如纳克/毫升的紫杉醇(Ptx))与天然安全的抗癌药物姜黄素(Cur)联合使用,以降低全身毒性,这是非常有利的。然而,Cur 和 Ptx 的生物利用度都很差。在此,通过疏水组装将两亲性聚合物 PF-127(P)功能化还原氧化石墨烯(G),构建了药物输送载体。通过 π-π 相互作用加载药物,得到尺寸为 140nm 的纳米级 GP-Cur-Ptx。实现了高达 678wt%的高 Cur 负载量,这是迄今为止任何其他 Cur 纳米制剂中最高的负载量。基于细胞增殖测定,GP-Cur-Ptx 是一种协同治疗(CI<1),对肺癌 A549(IC50=13.24μg/ml)和乳腺癌 MDA-MB-231(IC50=1.450μg/ml)细胞具有很高的功效。活性氧增加、线粒体膜电位耗竭和细胞凋亡进一步证实了这些积极的发现。相同剂量处理正常 MRC-5 细胞表明该系统具有生物相容性和癌细胞特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/cd1d863db499/srep32808-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/b5404455122e/srep32808-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/fd8fb935b802/srep32808-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/4e5de6dd0465/srep32808-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/cd1d863db499/srep32808-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/bc3f8ca8bb1d/srep32808-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/2fb1d31bf3b6/srep32808-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/0b28e299d664/srep32808-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/ab6c5904a072/srep32808-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/b5404455122e/srep32808-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/fd8fb935b802/srep32808-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/4e5de6dd0465/srep32808-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e683/5011726/cd1d863db499/srep32808-f8.jpg

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