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用于高负载未修饰阿霉素及阿霉素-雷帕霉素持续共释放的纳米多孔整体金

Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin.

作者信息

Bhattarai Jay K, Neupane Dharmendra, Nepal Bishal, Demchenko Alexei V, Stine Keith J

机构信息

Department of Chemistry and Biochemistry, University of Missouri-St. Louis, Saint Louis, MO 63121, USA.

出版信息

Nanomaterials (Basel). 2021 Jan 15;11(1):208. doi: 10.3390/nano11010208.

Abstract

Nanoparticles (NPs) have been widely explored for delivering doxorubicin (DOX), an anticancer drug, to minimize cardiotoxicity. However, their efficiency is marred by a necessity to chemically modify DOX, NPs, or both and low deposition of the administered NPs on tumors. Therefore, alternative strategies should be developed to improve therapeutic efficacy and decrease toxicity. Here we report the possibility of employing a monolithic nanoporous gold (np-Au) rod as an implant for delivering DOX. The np-Au has very high DOX encapsulation efficiency (>98%) with maximum loading of 93.4 mg cm without any chemical modification required of DOX or np-Au. We provide a plausible mechanism for the high loading of DOX in np-Au. The DOX sustained release for 26 days from np-Au in different pH conditions at 37 °C, which was monitored using UV-Vis spectroscopy. Additionally, we encased the DOX-loaded np-Au with rapamycin (RAPA)-trapped poly(D,L-lactide-co-glycolide) (PLGA) to fabricate an np-Au@PLGA/RAPA implant and optimized the combinatorial release of DOX and RAPA. Further exploiting the effect of the protein corona around np-Au and np-Au@PLGA/RAPA showed zero-order release kinetics of DOX. This work proves that the np-Au-based implant has the potential to be used as a DOX carrier of potential use in cancer treatment.

摘要

纳米颗粒(NPs)已被广泛研究用于递送阿霉素(DOX)这种抗癌药物,以将心脏毒性降至最低。然而,其效率受到需要对DOX、NPs或两者进行化学修饰以及所施用的NPs在肿瘤上的低沉积的影响。因此,应开发替代策略以提高治疗效果并降低毒性。在此,我们报告了采用整体式纳米多孔金(np-Au)棒作为递送DOX的植入物的可能性。np-Au具有非常高的DOX包封效率(>98%),最大负载量为93.4 mg/cm³,无需对DOX或np-Au进行任何化学修饰。我们为np-Au中DOX的高负载量提供了一种合理的机制。在37°C的不同pH条件下,DOX从np-Au中持续释放26天,这通过紫外-可见光谱法进行监测。此外,我们用包裹有雷帕霉素(RAPA)的聚(D,L-丙交酯-共-乙交酯)(PLGA)包裹负载DOX的np-Au,以制造np-Au@PLGA/RAPA植入物,并优化了DOX和RAPA的组合释放。进一步利用np-Au和np-Au@PLGA/RAPA周围蛋白质冠层的作用,显示出DOX的零级释放动力学。这项工作证明,基于np-Au的植入物有潜力用作癌症治疗中具有潜在用途的DOX载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5881/7830488/7057730f0382/nanomaterials-11-00208-sch001.jpg

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