Chen Xiangjun, Zhang Xiuping, Zhang Lingyu, Gao Yuzhou, Wang Changrong, Hong Wei, Zhao Guodong, Li Lu, Liu Rong, Wang Chungang
School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, P. R. China and Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin 130024, P. R. China.
Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital; Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, 100000, P. R. China.
Nanoscale. 2021 Feb 25;13(7):3974-3982. doi: 10.1039/d0nr09017d.
Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors worldwide. With unsatisfactory effects of traditional systematic chemotherapy for HCC owing to its drug resistance, novel therapeutic strategies based on nanomaterials for HCC treatments are promising solutions. To solve the challenges of nanoparticles (NPs)-based drug delivery systems for potential clinical applications, we designed water soluble amphiphilic oleic acid-NaYF4:Yb,Er/polydopamine Au nanoflower Janus NPs (OA-UCNPs/PDA-AuF JNPs) with discrete multi compartment nanostructures as dual-drug delivery systems (DDDSs). This unique nanostructure meets the requirements for containing hydrophobic hydroxycamptothecin/hydrophilic doxorubicin in divided spaces and releasing each drug from non-interfering channels under pH/near-infrared (NIR) dual-stimuli. The amphiphilic DDDSs were utilized to eradicate the tumor burden on a high-fidelity HCC model of a patient-derived xenograft (PDX), and represented an efficient strategy for defeating HCC using multi-modal imaging-guided dual-drug chemo-photothermal therapy in the second NIR window. In addition, the potential mechanisms of action for the DDDSs were evaluated.
肝细胞癌（HCC）是全球最常见且致命的恶性肿瘤之一。由于传统的系统性化疗对HCC存在耐药性，效果不尽人意，基于纳米材料的HCC新型治疗策略是很有前景的解决方案。为了解决基于纳米颗粒（NPs）的药物递送系统在潜在临床应用中的挑战，我们设计了具有离散多隔室纳米结构的水溶性两亲性油酸-NaYF4:Yb,Er/聚多巴胺金纳米花Janus纳米颗粒（OA-UCNPs/PDA-AuF JNPs）作为双药物递送系统（DDDSs）。这种独特的纳米结构满足了在分隔空间中包含疏水性羟基喜树碱/亲水性阿霉素，并在pH/近红外（NIR）双刺激下从互不干扰的通道释放每种药物的要求。两亲性DDDSs被用于消除患者来源异种移植（PDX）的高保真HCC模型上的肿瘤负担，并代表了一种在第二近红外窗口中使用多模态成像引导双药物化疗-光热疗法战胜HCC的有效策略。此外，还评估了DDDSs的潜在作用机制。
