An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery

• Published in: Biomaterials 2014-11, Vol.35 (34), p.9355-9362
• Main Authors: Chen, Qian, Liang, Chao, Wang, Xin, He, Jingkang, Li, Yonggang, Liu, Zhuang
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Albumins - chemistry; Albumins - therapeutic use; Animals; Contrast Media - chemistry; Dentistry; Female; Fluorescence; Gadolinium - pharmacology; Human albumin; Lymph node; Lymph Nodes - pathology; Lymphatic Metastasis - diagnosis; Lymphatic Metastasis - prevention & control; Magnetic Resonance Imaging; Mice; Mice, Nude; Multimodal imaging; Multimodal Imaging - methods; Nanostructures - chemistry; Nanostructures - therapeutic use; Neoplasms - surgery; Photothermal therapy; Protein Conformation; Treatment Outcome; Tumor metastasis
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2014.07.062

Abstract A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a ‘photothermal ablation assisted surgery’ strategy, promising for future clinical cancer treatment.