Huang Xueqin, Chen Lingzhi, Zhang Yuping, Zhou Suyan, Cai Huai-Hong, Li Ting, Jin Hua, Cai Jiye, Zhou Haibo, Pi Jiang
State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 000583, China.
Department of Chemistry, Jinan University, Guangzhou 510632, China.
Bioinorg Chem Appl. 2021 Mar 31;2021:5534870. doi: 10.1155/2021/5534870. eCollection 2021.
How to actively target tumor sites manipulating the controllable release of the encapsulated anticancer drugs and photosensitizers for synergistic anticancer therapy remains a big challenge. In this study, a cancer cell-targeted, near-infrared (NIR) light-triggered and anticancer drug loaded liposome system (LPs) was developed for synergistic cancer therapy. Photosensitizer indocyanine green (ICG) and chemotherapy drug Curcumin (CUR) were coencapsulated into the liposomes, followed by the surface conjugation of GE11 peptide for epidermal growth factor receptor (EGFR) targeting on the cancer cell surface. Strictly controlled by NIR light, GE11 peptide modified and CUR/ICG-loaded LPs (GE11-CUR/ICG-LPs) could introduce hyperthermia in EGFR overexpressed A549 cancer cells for photothermal therapy, which could also trigger the increased release of CUR for enhanced cancer cell inhibition. GE11-CUR/ICG-LPs synergized photochemotherapy could induce reactive oxygen species (ROS) generation and cytoskeleton disruption to activate stronger apoptotic signaling events than the photothermal therapy or chemotherapy alone by regulating Bax/Bcl-2 and PI3K/AKT pathways. This EGFR-targeted drug-delivery nanosystem with NIR sensitivity may potentially serve in more effective anticancer therapeutics with reduced off-target effects.
如何通过操控包封的抗癌药物和光敏剂的可控释放来积极靶向肿瘤部位以实现协同抗癌治疗仍然是一个巨大的挑战。在本研究中，开发了一种癌细胞靶向、近红外（NIR）光触发且负载抗癌药物的脂质体系统（LPs）用于协同癌症治疗。将光敏剂吲哚菁绿（ICG）和化疗药物姜黄素（CUR）共包封到脂质体中，随后在癌细胞表面进行表皮生长因子受体（EGFR）靶向的GE11肽的表面偶联。在近红外光的严格控制下，GE11肽修饰且负载CUR/ICG的LPs（GE11-CUR/ICG-LPs）可在EGFR过表达的A549癌细胞中引发热疗用于光热治疗，这也可触发CUR的释放增加以增强对癌细胞的抑制。GE11-CUR/ICG-LPs协同光化学疗法可诱导活性氧（ROS）生成和细胞骨架破坏，通过调节Bax/Bcl-2和PI3K/AKT途径比单独的光热疗法或化疗激活更强的凋亡信号事件。这种具有近红外敏感性的EGFR靶向药物递送纳米系统可能潜在地用于更有效的抗癌治疗，同时减少脱靶效应。
