Department of Biomaterials, Key Laboratory of Biomedical Engineering of Fujian Province, Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, State Key Lab of Physical Chemistry of Solid Surface, College of Materials, Xiamen University, Xiamen, 361005, P. R. China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnosis & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, P. R. China.
Adv Mater. 2018 Jul;30(28):e1707567. doi: 10.1002/adma.201707567. Epub 2018 May 22.
In recent years, hepatitis B core protein virus-like particle (HBc VLP) is an impressive biomaterial, which has attracted considerable attention due to favorable properties such as structural stability, high uptake efficiency, and biocompatibility in biomedical applications. Heretofore, only a few attempts have been made to apply it in physical, chemical, and biological therapy for cancer. In this study, a tumor-targeting RGD-HBc VLP is first fabricated through genetic engineering. For image-guided cancer phototherapy, indocyanine green (ICG) is loaded into RGD-HBc VLP via a disassembly/reassembly pathway and electrostatic attraction with high efficiency. The self-assembled stable RGD-HBc VLP significantly improves body retention (fourfold longer), aqueous stability, and target specificity of ICG. Remarkably, these positive reformations promote more accurate and sensitive imaging of U87MG tumor, as well as prolonged tumor destruction in comparison with free ICG. Moreover, the photothermal and photodynamic effect on tumors are quantitatively differentiated by multiple linear regression analysis. Overall, less-potent medicinal ICG can be perfectly rescued by bioengineered HBc VLP to realize enhanced cancer optotheranostics.
近年来，乙型肝炎核心蛋白病毒样颗粒（HBc VLP）是一种引人注目的生物材料，由于其结构稳定性、高摄取效率和生物相容性等优良特性，在生物医学应用中引起了相当大的关注。迄今为止，只有少数尝试将其应用于癌症的物理、化学和生物治疗。在本研究中，首先通过基因工程制备了一种肿瘤靶向 RGD-HBc VLP。为了进行图像引导的癌症光疗，吲哚菁绿（ICG）通过解组装/再组装途径和静电吸引力高效装载到 RGD-HBc VLP 中。自组装的稳定 RGD-HBc VLP 显著提高了 ICG 的体内保留（延长四倍）、水稳定性和靶向特异性。值得注意的是，与游离 ICG 相比，这些积极的改进促进了 U87MG 肿瘤更准确和更敏感的成像以及肿瘤的延长破坏。此外，还通过多元线性回归分析定量区分了肿瘤的光热和光动力效应。总的来说，通过生物工程 HBc VLP 可以完美地挽救药效较弱的药用 ICG，从而实现增强的癌症光热治疗。
