Details

Autor(en) / Beteiligte

• Wu, Chun-Yi
• Lin, Jia-Jia
• Chang, Wen-Yi
• Hsieh, Cheng-Ying
• Wu, Chin-Ching
• Chen, Hong-Sen
• Hsu, Hung-Ju
• Yang, An-Suei
• Hsu, Ming-Hua
• Kuo, Wei-Ying

Titel

Development of theranostic active-targeting boron-containing gold nanoparticles for boron neutron capture therapy (BNCT)

Ist Teil von

• Colloids and surfaces, B, Biointerfaces, 2019-11, Vol.183, p.110387, Article 110387

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •Novel Antibody-armed gold nanoparticle-boron cage assemblies were prepared for BNCT.•Noninvasive imaging was used to determine the pharmacokinetics of nanoparticles.•The level of radioactivity of tumor can reflect the boron content in tumor.•Antibody-mediated phagocytosis may dramatically increase tumor accumulation. Successful boron neutron capture therapy (BNCT) requires sufficient and specific delivery of boron atoms to malignant cells. Gold nanoparticles (AuNPs) have been used as a useful delivery system for selectively releasing cytotoxic payloads in the tumor. However, studies demonstrating the in vivo distribution or pharmacokinetics of boron-containing AuNPs via noninvasive imaging are lacking. This study aims to develop theranostic AuNP-boron cage assemblies (B-AuNPs) and evaluate its feasibility for BNCT. The commercial citrate-coated AuNPs were subjected to PEGylation, azide addition, and carborane modification on the surface. To further arm the AuNPs, we conjugated anti-HER2 antibody (61 IgG) with boron-containing PEGylated AuNPs to form 61-B-AuNPs. The diameter and radiolabeling efficiency of boron-containing AuNPs were determined by dynamic light scattering (DLS) and radio thin-layer chromatography (radio TLC), respectively. Noninvasive single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging was performed to determine the pharmacokinetics of radioiodinated AuNPs in N87 gastric cancer xenografts, and the content of boron in tumor and muscle was assessed by inductively coupled plasma mass spectrometry (ICP-MS). After the 3-step modification, the diameter of B-AuNPs increased by ˜25 nm, and antibody conjugation did not affect the diameter of AuNPs. Radioactive iodine (I-123) was introduced in AuNPs by Click chemistry under copper catalysis. The radiolabeling efficiency of 123I-B-AuNPs and 123I-61-B-AuNPs was approximately 60 ± 5%. After purification, the radiochemical purity (RCP) of these NPs was greater than 90%. MicroSPECT/CT imaging showed that the tumor-to-muscle (T/M) ratio of 123I-B-AuNP-injected mice reached 1.91 ± 0.17 at 12 h post-injection, while that of 123I-61-B-AuNP-injected mice was 12.02 ± 0.94. However, the increased uptake of AuNPs by the thyroid was observed at 36 h after the administration of 123I-61-B-AuNPs, indicating antibody-mediated phagocytosis. The T/M ratio, assessed by ICP-MS, of B-AuNP- and 61-B-AuNP-injected mice was 4.91 ± 2.75 and 41.05 ± 11.15, respectively. We successfully developed detectable HER2-targeting boron-containing AuNPs with high RCP and an acceptable yield. Noninvasive imaging could be a valuable tool for the noninvasive determination of the pharmacokinetics of AuNPs and measurement of boron concentration in the tumor.