Abstract

Nano graphene oxide (NGO) has high drug-loading capacity due to its huge surface area. However, the limited stability and the poor biocompatibility of NGO hampered its application as drug delivery carrier under physiological conditions. Thereby, a new strategy of using chemical conjugation on NGO with hydrophilic polymers was adopted but currently was too complicated, low yield and costly. In this study, doxorubicin-hyd-PEG-folic acid (DOX-hyd-PEG-FA) polymers were coated on the surface of NGO via π–π stocking and the hydrophobic effect between DOX and NGO. With the PEG shell protection, the biocompatibility of NGO was significantly improved. The drug-loading capacity of nanoparticles was more than 100%. FA ligands on the nanoparticle could guide the nanoparticles actively targeting to tumour cells. The hydrazone bond between DOX and PEG was decomposed spontaneously in the weakly acidic environment, which made PEG layer dissociated from NGO. Furthermore, DOX was easily protonized at low pH conditions, which weakened the interaction between DOX and NGO. Thus, DOX could be released rapidly from the nanoparticles in tumour cells. In summary, NGO@DOX-hyd-PEG-FA is an easy-prepared nanoparticle with excellent biocompatibility, high pH-sensitivity and active tumour targeting. Therefore, it is a promising multifunctional nanocarrier effective for targeted drug delivery.

摘要

纳米氧化石墨烯（NGO）由于其巨大的表面积而具有很高的载药能力。然而，非政府组织有限的稳定性和较差的生物相容性阻碍了其在生理条件下作为药物递送载体的应用。因此，采用了一种新的策略，即在 NGO 上使用亲水性聚合物进行化学共轭，但目前过于复杂、收率低且成本高。在这项研究中，阿霉素-HYD-PEG-叶酸（DOX-HYD-PEG-FA）聚合物涂布非政府组织的表面上通过π-π 放养和 DOX 和 NGO 之间的疏水效应。通过PEG外壳保护，NGO的生物相容性显着提高。纳米颗粒的载药能力大于100%。纳米颗粒上的FA配体可以引导纳米颗粒主动靶向肿瘤细胞。DOX与PEG之间的腙键在弱酸性环境中自发分解，使PEG层与NGO解离。此外，DOX 在低 pH 条件下容易质子化，从而削弱了 DOX 与 NGO 之间的相互作用。因此，DOX 可以从肿瘤细胞中的纳米颗粒中迅速释放。总之，NGO@DOX-hyd-PEG-FA 是一种易于制备的纳米颗粒，具有优异的生物相容性、高 pH 敏感性和活性肿瘤靶向性。所以，