RGD-Human Serum Albumin Conjugates as Efficient Tumor Targeting Probes
Cyclic arginine-glycine-aspartate (RGD) peptides and their derivatives have been intensively studied as tumor targeting probes. One major drawback, however, is their short blood circulation half-lives, which greatly compromises their targeting efficacy. To address this issue, a cyclic peptide, c(RGD...
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SAGE Publishing
2009-03-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2009.00011 |
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| author | Kai Chen Jin Xie Xiaoyuan Chen |
| author_facet | Kai Chen Jin Xie Xiaoyuan Chen |
| author_sort | Kai Chen |
| collection | DOAJ |
| description | Cyclic arginine-glycine-aspartate (RGD) peptides and their derivatives have been intensively studied as tumor targeting probes. One major drawback, however, is their short blood circulation half-lives, which greatly compromises their targeting efficacy. To address this issue, a cyclic peptide, c(RGDyK), and an organic dye (IRDye800 or Cy5.5) were covalently conjugated onto human serum albumin (HSA). The conjugates were subjected to in vitro cell staining, in vivo near-infrared fluorescence (NIRF) imaging, ex vivo NIRF imaging, and histologic studies to evaluate their feasibility as tumor imaging probes. As a control, RAD peptide was also coupled with HSA and labeled with IRDye800 for in vivo imaging. The HSA-RGD-IRDye800 exhibited integrin α v β 3 -specific binding in cell staining experiment. In vivo NIRF imaging showed higher tumor accumulation and tumor to background contrast of HSA-RGD-IRDye800 over RGD-IRDye800. The integrin specificity of HSA-RGD-IRDye800 is confirmed by both successful inhibition of tumor uptake in the presence of c(RGDyK) and the inability to accumulate in integrin-positive tumors by RAD-HSA-IRDye800. Histologic examination revealed initial tumor vascular binding and eventually both tumor vasculature and tumor cell integrin binding in vivo. In summary, we successfully developed an RGD-based protein conjugate with prolonged circulation half-life for NIRF imaging of tumor integrin α v β 3 expression. The success of this study may be generalizable for other peptide-based probes to be conjugated with HSA for prolonged tumor contrast and improved pharmacokinetics. |
| format | Article |
| id | doaj-art-faf2bc10bd4d4bf9ae8b1647e4ae0d69 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2009-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-faf2bc10bd4d4bf9ae8b1647e4ae0d692025-01-02T22:37:56ZengSAGE PublishingMolecular Imaging1536-01212009-03-01810.2310/7290.2009.0001110.2310_7290.2009.00011RGD-Human Serum Albumin Conjugates as Efficient Tumor Targeting ProbesKai ChenJin XieXiaoyuan ChenCyclic arginine-glycine-aspartate (RGD) peptides and their derivatives have been intensively studied as tumor targeting probes. One major drawback, however, is their short blood circulation half-lives, which greatly compromises their targeting efficacy. To address this issue, a cyclic peptide, c(RGDyK), and an organic dye (IRDye800 or Cy5.5) were covalently conjugated onto human serum albumin (HSA). The conjugates were subjected to in vitro cell staining, in vivo near-infrared fluorescence (NIRF) imaging, ex vivo NIRF imaging, and histologic studies to evaluate their feasibility as tumor imaging probes. As a control, RAD peptide was also coupled with HSA and labeled with IRDye800 for in vivo imaging. The HSA-RGD-IRDye800 exhibited integrin α v β 3 -specific binding in cell staining experiment. In vivo NIRF imaging showed higher tumor accumulation and tumor to background contrast of HSA-RGD-IRDye800 over RGD-IRDye800. The integrin specificity of HSA-RGD-IRDye800 is confirmed by both successful inhibition of tumor uptake in the presence of c(RGDyK) and the inability to accumulate in integrin-positive tumors by RAD-HSA-IRDye800. Histologic examination revealed initial tumor vascular binding and eventually both tumor vasculature and tumor cell integrin binding in vivo. In summary, we successfully developed an RGD-based protein conjugate with prolonged circulation half-life for NIRF imaging of tumor integrin α v β 3 expression. The success of this study may be generalizable for other peptide-based probes to be conjugated with HSA for prolonged tumor contrast and improved pharmacokinetics.https://doi.org/10.2310/7290.2009.00011 |
| spellingShingle | Kai Chen Jin Xie Xiaoyuan Chen RGD-Human Serum Albumin Conjugates as Efficient Tumor Targeting Probes Molecular Imaging |
| title | RGD-Human Serum Albumin Conjugates as Efficient Tumor Targeting Probes |
| title_full | RGD-Human Serum Albumin Conjugates as Efficient Tumor Targeting Probes |
| title_fullStr | RGD-Human Serum Albumin Conjugates as Efficient Tumor Targeting Probes |
| title_full_unstemmed | RGD-Human Serum Albumin Conjugates as Efficient Tumor Targeting Probes |
| title_short | RGD-Human Serum Albumin Conjugates as Efficient Tumor Targeting Probes |
| title_sort | rgd human serum albumin conjugates as efficient tumor targeting probes |
| url | https://doi.org/10.2310/7290.2009.00011 |
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