Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance.
Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance.
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DOI：
10.1038/s41467-020-20588-0
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发表时间：
2021-01-12
影响因子：
16.6
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Wang H;Liang Y;Yin Y;Zhang J;Su W;White AM;Bin Jiang;Xu J;Zhang Y;Stewart S;Lu X;He X
跨膜P-糖蛋白（P-gp）泵外排药物是肿瘤耐药的主要机制。它们在保护正常组织细胞免受有毒的外源性物质和内源性代谢物的影响方面也很重要。在这里，我们报告了岩藻聚糖修饰的二氧化硅-碳纳米洋葱（FSCNO）混合纳米颗粒，靶向肿瘤血管系统特异性释放P-gp抑制剂和抗癌药物进入肿瘤细胞。使用多种模型证明了纳米颗粒的肿瘤血管靶向能力。此外，我们揭示了纳米洋葱在近红外区域（NIR）的上级光吸收特性，这使得在低NIR功率下从纳米颗粒触发药物释放成为可能。释放的抑制剂选择性地与P-gp泵结合并使其功能丧失，这提高了细胞内抗癌药物的生物利用度。此外，游离P-gp抑制剂显著增加化疗药物的全身毒性，这可以通过将它们与FSCNO纳米颗粒结合短时间低功率NIR激光照射来解决。已知跨膜P-糖蛋白（P-gp）泵通过增强药物外排而促进耐药性。在这里，作者使用肿瘤血管靶向纳米颗粒递送P-gp抑制剂和化疗剂，以克服耐药性。
The transmembrane P-glycoprotein (P-gp) pumps that efflux drugs are a major mechanism of cancer drug resistance. They are also important in protecting normal tissue cells from poisonous xenobiotics and endogenous metabolites. Here, we report a fucoidan-decorated silica-carbon nano-onion (FSCNO) hybrid nanoparticle that targets tumor vasculature to specifically release P-gp inhibitor and anticancer drug into tumor cells. The tumor vasculature targeting capability of the nanoparticle is demonstrated using multiple models. Moreover, we reveal the superior light absorption property of nano-onion in the near infrared region (NIR), which enables triggered drug release from the nanoparticle at a low NIR power. The released inhibitor selectively binds to P-gp pumps and disables their function, which improves the bioavailability of anticancer drug inside the cells. Furthermore, free P-gp inhibitor significantly increases the systemic toxicity of a chemotherapy drug, which can be resolved by delivering them with FSCNO nanoparticles in combination with a short low-power NIR laser irradiation. The transmembrane P-glycoprotein (P-gp) pumps are known to promote drug resistance by enhancing drug efflux. Here, the authors deliver P-gp inhibitor and a chemotherapeutic agent using tumor blood vessel-targeting nanoparticle, to overcome drug resistance.
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纳米碗支持的脂质体改善药物装载和递送
影响因子：
10.8
作者：
Chen, Zhong-Jian;Yang, Si-Cong;Fang, Chao
通讯作者：
Fang, Chao
影响因子：
16.6
作者：
Honkura N;Richards M;Laviña B;Sáinz-Jaspeado M;Betsholtz C;Claesson-Welsh L
通讯作者：
Claesson-Welsh L
DOI：
10.1126/science.1168750
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Aller SG;Yu J;Ward A;Weng Y;Chittaboina S;Zhuo R;Harrell PM;Trinh YT;Zhang Q;Urbatsch IL;Chang G
通讯作者：
Chang G
影响因子：
64.5
作者：
Lambert AW;Pattabiraman DR;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
17.1
作者：
Liu, Zhuang;Sun, Xiaoming;Dai, Hongjie
通讯作者：
Dai, Hongjie