Doxorubicin Stability and Retention on PEGylated Graphene Oxide Nanocarriers Adjacent to Human Serum Albumin

Drug
stability and retention on nanocarriers is essential for maximizing
the drug targeting and therapeutic efficiency. PEGylation of graphene
oxide (GO) as a drug nanocarrier is widely known to prolong its circulation
time in the body, thereby increasing the probability of drug delivery
system interactions with the proteins in the blood stream. Herein,
molecular dynamics (MD) simulations were performed to investigate
the interactions between doxorubicin (DOX)-loaded GO and PEGylated
GO (PEGGO) nanocarriers with human serum albumin (HSA), a prevalent
human blood protein and among the first to be adsorbed on the DOX-loaded
nanocarriers. The results indicate that drug stability and retention
on PEGGO nanocarriers are far more superior to the GO nanocarriers
(control) when in contact with HSA. It is also demonstrated in this
work that the PEGGO nanocarriers retain the DOX molecules irrespective
of the HSA Sudlow site I and II orientations, thereby revealing their
robustness in DOX loading.

纳米载体上的药物稳定性与保留率，对于最大化药物靶向性与治疗效能至关重要。将作为药物纳米载体的氧化石墨烯（graphene oxide, GO）进行聚乙二醇化（PEGylation）修饰，已被广泛证实可有效延长其体内循环时间，进而提升药物递送系统与血液中蛋白质相互作用的概率。本研究通过分子动力学（molecular dynamics, MD）模拟，探究了负载阿霉素（doxorubicin, DOX）的GO与聚乙二醇化GO（PEGGO）纳米载体，与人血清白蛋白（human serum albumin, HSA，一种主要的人体血液蛋白，也是首批吸附于负载DOX的纳米载体的蛋白之一）之间的相互作用。研究结果表明，与作为对照的GO纳米载体相比，PEGGO纳米载体在与HSA接触时，药物稳定性与保留率显著更优。本研究同时证实，无论HSA的Sudlow位点I与II朝向如何，PEGGO纳米载体均能保留DOX分子，由此揭示了其在DOX负载方面的优异稳定性。