Wang, Zhen, Cheng, Hao, Sheng, Yu, Chen, Zongkai, Zhu, Xiaohong, Ren, Jianye, Zhang, Xiangze, Lv, Lingyu, Zhang, Huaqing, Zhou, Jianping, and Ding, Yang
Biofunctional surface-modification surpassed critical limitation of graphene oxide (GO) in biocompatibility and drug delivery efficiency, contributing to versatile biomedical applications. Here, a protein corona-bridged GO nanoplatform with high drug loading, longstanding hyperthermia, and controllable drug release, was engineered for amplified tumor therapeutic benefits. Structurally, GO surface was installed with phenylboronic acid (PBA) layer, on which iRGD conjugated apolipoprotein A-I (iRGD-apoA-I) was coordinated via boron electron-deficiency, to form the sandwich-like GO nanosheet (iAPG). The GO camouflaging by iRGD-apoA-I corona provided multimodal high doxorubicin (DOX) loading by π-π stacking and coordination, and generated a higher photothermal transformation efficiency simultaneously. In vitro studies demonstrated that iAPG significantly improved drug penetration and internalization, then achieved tumor-targeted DOX release through near-infrared (NIR) controlled endo/lysosome disruption. Moreover, iAPG mediated site-specific drug shuttling to produce a 3.53-fold enhancement of tumor drug-accumulation compared to the free DOX in vivo , and induced deep tumor penetration dramatically. Primary tumor ablation and spontaneous metastasis inhibition were further demonstrated with negligible side effects under optimal NIR. Taken together, our work provided multifunctional protein corona strategy to inorganic nanomaterials toward advantageous biomedical applications. [ABSTRACT FROM AUTHOR]