Biofunctionalized graphene oxide nanosheet for amplifying antitumor therapy: Multimodal high drug encapsulation, prolonged hyperthermal window, and deep-site burst drug release.

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.

High KIAA1522 expression predicts a poor prognosis in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor associated with a poor prognosis, and the molecular mechanisms remain poorly understood. KIAA1522 expression is upregulated in various types of tumor tissue; however, its function remains unknown in HCC. Bioinformatics analysis was undertaken using Oncomine, OncoLnc and other databases, in order to determine KIAA1522 expression in HCC and to analyze its association with postoperative prognosis. Reverse transcription-quantitative PCR was performed to detect KIAA1522 mRNA expression in primary HCC and adjacent normal tissues, while KIAA1522 protein expression was assessed via immunohistochemical staining. KIAA1522 expression and clinicopathological characteristics of primary HCC were evaluated, and their association with patient prognosis was analyzed. The Oncomine database results indicated that KIAA1522 expression in HCC and normal liver tissues was significantly different. RT-qPCR analysis demonstrated that KIAA1522 mRNA expression was significantly higher in HCC tissues compared with that in adjacent normal tissues. Immunohistochemical analysis indicated that expression rate of KIAA1522 protein was significantly higher in primary HCC tissues compared with that in normal liver tissues. The OncoLnc database results demonstrated that KIAA1522 expression was significantly associated with short-term survival. Kaplan-Meier survival analysis indicated that high KIAA1522 protein expression was significantly associated with short-term survival for patients with HCC. Multivariate Cox regression analysis demonstrated that tumor size, Tumor-Node-Metastasis stage and high KIAA1522 protein expression were independent predictors of a poor prognosis in patients with primary HCC. Furthermore, high KIAA1522 expression was significantly associated with postoperative survival time in primary HCC, and thus may be a potential molecular marker for prognosis in patients with this cancer type.