National Engineering Research Center for Nanomedicine, Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics & Moe Key Laboratory of Biomedical Photonics of Ministry of Education, Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.
Theranostics. 2018 Oct 24;8(19):5362-5378. doi: 10.7150/thno.27631. eCollection 2018.
Gold nanocages (AuNCs), with high photothermal conversion efficiency and unique hollow interiors, have become a promising nanoplatform for synergistic phototheraml therapy (PTT)-chemotherapy. However, the insufficient tumor targeting, in vivo premature drug leakage and low drug loading efficiency responsible for the spatial-temporal un-synchronization of PTT-chemotherapy, as well as inflammatory response might compromise the anticancer treatment of AuNCs-based drug delivery systems. Cancer cell membrane (CCM)-coated AuNCs were developed to load anticancer drug doxorubicin (DOX@CAuNCs) by transmembrane ammonium sulfate gradient method. In vitro and in vivo analysis, including characterization, macrophage phagocytosis and tumor targeting capacity, near-infrared (NIR) laser-induced drug release, antitumor efficacy and inflammation response were systematically performed. DOX@CAuNCs showed a high DOX loading capacity and on-demand NIR laser-triggered DOX release compared with CAuNCs passively loading DOX by electrostatic adsorption, a commonly used method to load drug to AuNCs. Meanwhile, in view of the properties of CCM coated on AuNCs, DOX@CAuNCs exhibited decreased macrophage phagocytosis, prolonged blood circulation and enhanced internalization by cancer cells, generating preferable tumor targeting ability. With these integrated advantages, DOX@CAuNCs demonstrated highly efficient and precise spatial-temporal synchronization of PTT-chemotherapy, achieving complete tumor ablation with no obvious side effects. Besides, coating with CCM significantly alleviated AuNCs-induced inflammatory response. This biomimetic AuNCs-based platform might be a prospective drug delivery system for precision PTT and chemotherapy, acquiring desired cancer treatment efficacy and low inflammatory response.
金纳米笼 (AuNCs) 具有高光热转换效率和独特的中空内部，已成为协同光热治疗 (PTT)-化学疗法的有前途的纳米平台。然而，肿瘤靶向不足、体内药物过早泄漏和载药效率低导致 PTT-化学疗法的时空不同步，以及炎症反应可能会影响基于 AuNCs 的药物递送系统的抗癌治疗效果。通过跨膜硫酸铵梯度法，开发了具有癌细胞膜 (CCM) 涂层的 AuNCs 来负载抗癌药物阿霉素 (DOX@CAuNCs)。进行了体外和体内分析，包括表征、巨噬细胞吞噬和肿瘤靶向能力、近红外 (NIR) 激光诱导的药物释放、抗肿瘤功效和炎症反应。与通过静电吸附被动负载 DOX 的 CAuNCs 相比，DOX@CAuNCs 具有高 DOX 载药能力和按需 NIR 激光触发 DOX 释放，静电吸附是一种常用于负载药物到 AuNCs 的方法。同时，鉴于 AuNCs 上涂覆的 CCM 的特性，DOX@CAuNCs 表现出降低的巨噬细胞吞噬作用、延长的血液循环和增强的癌细胞内化，从而产生更好的肿瘤靶向能力。具有这些综合优势，DOX@CAuNCs 实现了 PTT-化学疗法的高效和精确时空同步，具有完全的肿瘤消融作用，没有明显的副作用。此外，CCM 的涂层显著减轻了 AuNCs 引起的炎症反应。这种仿生 AuNCs 基平台可能是一种用于精确 PTT 和化疗的有前途的药物递送系统，可获得理想的癌症治疗效果和低炎症反应。
