Enhanced immunotherapy of SM5-1 in hepatocellular carcinoma by conjugating with gold nanoparticles and its in vivo bioluminescence tomographic evaluation

Abstract

SM5-1 is a humanized mouse monoclonal antibody, targeting an over-expressed membrane protein of approximately 230 kDa in hepatocellular carcinoma (HCC). SM5-1 can be used for target therapy in hepatocellular carinoma due to its ability of inhibiting cell growth and inducing apoptosis. However, the tumor inhibition efficacy of SM5-1 in HCC cancer treatment remains low. In this study, we synthesized SM5-1-conjugated gold nanoparticles (Au-SM5-1 NPs) and investigated their anticancer efficacy in HCC both in vitro and in vivo. The tumor inhibition rates of Au-SM5-1 NPs for subcutaneous tumor mice were 40.10% ± 4.34%, 31.37% ± 5.12%, and 30.63% ± 4.87% on day 12, 18, and 24 post-treatment as determined by bioluminescent intensity. In addition, we investigated the antitumor efficacy of Au-SM5-1 NPs in orthotopic HCC tumor models. The results showed that the inhibition rates of Au-SM5-1 NPs can reach up to 39.64% ± 4.87% on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, three-dimensional reconstruction results of the orthotopic tumor revealed that Au-SM5-1 NPs significantly inhibited tumor growth compared with SM5-1 alone. Our results suggested that the developed Au-SM5-1 NPs has great potential as an antibody-based nano-drug for HCC therapy.

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

“…142 The membrane protein is specifically expressed on HCC, melanoma, and breast cancer cells, indicating that it is a promising binding site of NPs for diagnosis and therapy of HCC. [143][144][145] Kou et al 146 fabricated negatively charged PTX-loaded poly(lactide-co-glycolide) (PLGA) NPs and then successfully coated them with cationic polypeptide polylysine fused to SM5-1 single-chain antibody (SM5-1 scFv), which was derived from SM5-1 mAb. The results demonstrated that the nanosystem retained high specific affinity to SM5-1 binding protein and could induce specific and efficient death of SM5-1 binding protein-positive Ch-hep-3 cells.…”

Long non-coding RNA AB019562 promotes cell proliferation and metastasis in human hepatocellular carcinoma

“…The most refractory limitation in the early detection and prevention of HCC is the absence of symptoms (22). Therefore, an increasing number of studies have focused on identifying novel biomarkers, which can be used to diagnose and prevent HCC in the early stage (23,24). …”

Nanomedicine approaches to improve cancer immunotherapy

“…Ma et al synthesized SM5‐1‐conjugated Au NPs (Au‐SM5‐1 NPs) and investigated their anticancer efficacy in hepatocellular carcinoma. Compared with SM5‐1 alone, Au‐SM5‐1 NPs significantly inhibited tumor growth of both subcutaneous and orthotopic hepatocellular carcinoma tumor models . Taken together, Au NPs‐based vaccines are promising nanocarriers for the delivery of TAAs and may act as an alternative self‐adjuvant.…”