Preparation and preliminary evaluation of hepatitis B core antigen virus like nanoparticles loaded with indocyanine green

Yunlong Wang; Yiqing Zhang; Yinyin Yu; Lei Ren; Jichuang Wang; Lei Cheng; Dandan Jiang; Xiangqian Guo; Tieshan Teng; Xiaoyong Luo; Shuangyu Lv; Xudong Wang; Huirui Wang; Xinpeng Shi; Heng Zhang; Shengli Bi

doi:10.21037/atm-20-7478

Preparation and preliminary evaluation of hepatitis B core antigen virus like nanoparticles loaded with indocyanine green

Ann Transl Med. 2020 Dec;8(24):1661. doi: 10.21037/atm-20-7478.

Authors

Yunlong Wang^{1

2}, Yiqing Zhang^{1

2}, Yinyin Yu³, Lei Ren⁴, Jichuang Wang¹, Lei Cheng¹, Dandan Jiang¹, Xiangqian Guo⁵, Tieshan Teng⁵, Xiaoyong Luo², Shuangyu Lv⁵, Xudong Wang³, Huirui Wang⁶, Xinpeng Shi⁶, Heng Zhang³, Shengli Bi¹

Affiliations

¹ Henan Bioengineering Research Center, Zhengzhou, China.
² Zhengzhou Technical College, Zhengzhou, China.
³ Henan General Hospital, Zhengzhou, China.
⁴ Department of Biomaterials, Key Laboratory of Biomedical Engineering of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surface, College of Materials, Xiamen University, Xiamen, China.
⁵ School of Basic Medical Sciences, Henan University, Kaifeng, China.
⁶ Department of Radiation Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China.

Abstract

Background: In recent years, nanotechnology has attracted a plethora of attention due of its ability to effectively diagnose and treat various tumors. Virus-like particles (VLPs) have good biocompatibility, are safe and non-toxic, and have an internal hollow space, and as such they are often used as nano drug carriers. In recent years, it has become one of the hot spots in the field of biopharmaceutical engineering.

Methods: In this study, the tumor-targeting peptide RGD (Arg-Gly-Asp) was genetically inserted into the major immunodominant region (MIR) of the hepatitis B virus core protein (HBc). A series of characterization, including stability and optical properties, were evaluated. A visual diagnosis and analysis of the efficacy against tumor cells were conducted at the cell level and using a live animal model.

Results: This study demonstrated that the recombinant HBc-based VLPs could participate in self-assembly of monodispersed nanoparticles with well-defined morphology, and the near-infrared dye indocyanine green (ICG) could be packaged into the VLPs without any chemical modification. Moreover, the HBc-based VLPs could specifically target cancer cells via the interaction with overexpressed integrin αvβ3. The treatment with ICG-loaded HBc-based VLPs showed significant inhibition of 4T1 breast cancer cell growth (84.87% tumor growth inhibition). The in vivo imaging experiments demonstrated that the ICG-loaded HBc-based VLPs generated excellent fluorescence in tumor sites in 4T1 breast cancer bearing mice. This provided crucial information on tumor mass location, boundaries, and shape. Moreover, compared to free ICG, the nanosystem showed significantly longer blood circulation time and superior accuracy in targeting the tumor.

Conclusions: The ICG-loaded HBc-based VLPs prepared in this study were of good stability and biocompatibility. It showed strong tumor targeting specificity and tumor visualization. Thus, it is expected to provide a new experimental basis and theoretical support for the integration of VLPs in the clinical diagnosis and treatment of breast cancer.

Keywords: Hepatitis B core protein (HBc); breast cancer; drug delivery; tumor targeting; virus-like particles (VLPs).