College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, China.
Department of Anesthesiology, The First Affiliated Hospital, Zhengzhou University , Zhengzhou 450002, China.
ACS Appl Mater Interfaces. 2018 Feb 21;10(7):6608-6617. doi: 10.1021/acsami.7b16910. Epub 2018 Feb 7.
A novel graphene oxide nanoparticle (GON)-based drug delivery system containing GONs as carriers of anticancer drugs and chitosan/dimethylmaleic anhydride-modified chitosan (CS/CS-DMMA) as surface charge-reversible shells is fabricated via the classic self-assembly of the deprotonated carboxyl of GONs and the protonated amine of the CS backbone by electrostatic interaction, and CS-DMMA serves as the outmost layer. In this GON-based drug delivery system, the GON cores as desired carriers might adsorb doxorubicin hydrochloride (DOX) via the π-π stacking interaction between the large π conjugated structures of GO and the aromatic structure of DOX. Meanwhile, the chitosan-based polyelectrolyte shells served as a smart protection screen to evade the premature release of the as-loaded DOX in normal extracellular condition, and then, the release of DOX was accelerated because of the detachment of chitosan coating at low pH. Furthermore, the re-exposure of amino groups after hydrolysis of CS-DMMA endowed the drug delivery system with positive surface charge by taking advantage of the pH difference between physiological conditions and the tumor microenvironment to enhance the cellular uptake. Then, the pH-dependent site-specific drug release was realized. The in vitro investigations confirmed that these promising GON/CS/CS-DMMA hybrids with the charge-reversible character possessed various merits including excellent encapsulation efficiency, high stability under physiological conditions, enhanced cellular uptake by HepG2 cells, and tunable intracellular chemotherapeutic agent release profiles, proving its capability as an intelligent anticancer agent nanocarrier with enhanced therapeutic effects. This smart GON/CS/CS-DMMA vehicle with the surface charge-reversible character may be used as a significant drug delivery system for cancer treatment.
一种新型的基于氧化石墨烯纳米粒子（GON）的药物传递系统，包含 GON 作为抗癌药物的载体和壳聚糖/马来酸二甲酯改性壳聚糖（CS/CS-DMMA）作为表面电荷可逆壳，通过 GON 去质子化羧基与 CS 主链质子化氨基之间的静电相互作用进行经典的自组装来制备，CS-DMMA 作为最外层。在这种基于 GON 的药物传递系统中，GON 核作为所需载体可能通过 GO 的大π共轭结构与 DOX 的芳香结构之间的π-π堆积相互作用吸附盐酸多柔比星（DOX）。同时，基于壳聚糖的聚电解质壳作为智能保护屏，以避免在正常细胞外条件下载药 DOX 的过早释放，然后由于壳聚糖涂层在低 pH 值下的脱落，加速了 DOX 的释放。此外，CS-DMMA 水解后重新暴露的氨基利用生理条件和肿瘤微环境之间的 pH 差异赋予药物传递系统正表面电荷，从而增强细胞摄取。然后，实现了 pH 依赖性的靶向药物释放。体外研究证实，这些具有电荷可逆特性的有前途的 GON/CS/CS-DMMA 混合物具有各种优点，包括出色的包封效率、在生理条件下的高稳定性、通过 HepG2 细胞增强的细胞摄取和可调的细胞内化疗药物释放特性，证明了其作为具有增强治疗效果的智能抗癌剂纳米载体的能力。这种具有表面电荷可逆特性的智能 GON/CS/CS-DMMA 载体可用作癌症治疗的重要药物传递系统。
