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

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number110387
JournalColloids and Surfaces B: Biointerfaces
Volume183
DOIs
Publication statusPublished - 2019 Nov 1

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Boron Neutron Capture Therapy
Boron
Gold
Nanoparticles
therapy
Neutrons
boron
gold
neutrons
nanoparticles
Pharmacokinetics
Tumors
tumors
muscles
antibodies
Antibodies
mice
Muscle
Imaging techniques
Inductively coupled plasma mass spectrometry

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

Cite this

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. / Development of theranostic active-targeting boron-containing gold nanoparticles for boron neutron capture therapy (BNCT). In: Colloids and Surfaces B: Biointerfaces. 2019 ; Vol. 183.
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abstract = "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.",
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Development of theranostic active-targeting boron-containing gold nanoparticles for boron neutron capture therapy (BNCT). / 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.

In: Colloids and Surfaces B: Biointerfaces, Vol. 183, 110387, 01.11.2019.

Research output: Contribution to journalArticle

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T1 - Development of theranostic active-targeting boron-containing gold nanoparticles for boron neutron capture therapy (BNCT)

AU - Wu, Chun Yi

AU - Lin, Jia Jia

AU - Chang, Wen Yi

AU - Hsieh, Cheng Ying

AU - Wu, Chin Ching

AU - Chen, Hong Sen

AU - Hsu, Hung Ju

AU - Yang, An Suei

AU - Hsu, Ming Hua

AU - Kuo, Wei Ying

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

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