TY - JOUR
T1 - PEGylated peptide to TIP1 is a novel targeting agent that binds specifically to various cancers in vivo
AU - Kapoor, Vaishali
AU - Singh, Abhay Kumar
AU - Rogers, Buck E.
AU - Thotala, Dinesh
AU - Hallahan, Dennis E.
N1 - Funding Information:
This work was supported by National Cancer Institute grants 1R01CA140220-02 , 5R01CA125757-06 , 7R01CA112385-0 (D. Hallahan), Siteman Cancer Research Award , Elizabeth and James McDonnell III Endowment (D. Hallahan), American Association for Cancer Research Grant 12-60-26-HALL (D. Hallahan), The Barnes-Jewish Hospital Foundation (BJHF) and the Washington University Institute of Clinical and Translational Sciences (ICTS) grant (D. Hallahan), Department of Radiation Oncology Startup Funds (D. Thotala).
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/3/28
Y1 - 2019/3/28
N2 - Targeted molecular imaging allows specific visualization and monitoring of tumors. Cancer-specific peptides have been developed for imaging and therapy. Peptides that specifically target cancer have several advantages including, ease of synthesis, low antigenicity, and enhanced diffusion into tissues. We developed the HVGGSSV peptide as a molecular targeting/imaging agent. HVGGSSV targets Tax interacting protein 1 (TIP1) which is a 14 kDa PDZ domain-containing protein that is overexpressed in cancer. We docked HVGGSSV in silico using the three-dimensional structure of TIP1 and found the binding energy was −6.0 kCal/mol. The binding affinity of HVGGSSV to TIP1 protein was found to have a K D of 3.3 × 10 −6 M using surface plasmon resonance. We conjugated a 40 kDa PEG to HVGGSSV to enhance the circulation and evaluated the tumor binding in nude mice bearing heterotopic cervical (HT3), esophageal (OE33), pancreatic (BXPC3), lung (A549) and glioma (D54) tumors. NanoSPECT/CT imaging of the mice was performed 48 h and 72 h after injecting with 111 Indium ( 111 In) labeled PEG-HVGGSSV or PEG-control peptide. SPECT imaging revealed that 111 In-PEG-HVGGSSV specifically bound to cervical, esophageal, pancreatic, lung and brain tumors. Post SPECT biodistribution data further validated tumor-specific binding. Overall, HVGGSSV peptide specifically binds to the major groove of the TIP1 protein surface. PEGylated-HVGGSSV could be used to target cancers that overexpress TIP1.
AB - Targeted molecular imaging allows specific visualization and monitoring of tumors. Cancer-specific peptides have been developed for imaging and therapy. Peptides that specifically target cancer have several advantages including, ease of synthesis, low antigenicity, and enhanced diffusion into tissues. We developed the HVGGSSV peptide as a molecular targeting/imaging agent. HVGGSSV targets Tax interacting protein 1 (TIP1) which is a 14 kDa PDZ domain-containing protein that is overexpressed in cancer. We docked HVGGSSV in silico using the three-dimensional structure of TIP1 and found the binding energy was −6.0 kCal/mol. The binding affinity of HVGGSSV to TIP1 protein was found to have a K D of 3.3 × 10 −6 M using surface plasmon resonance. We conjugated a 40 kDa PEG to HVGGSSV to enhance the circulation and evaluated the tumor binding in nude mice bearing heterotopic cervical (HT3), esophageal (OE33), pancreatic (BXPC3), lung (A549) and glioma (D54) tumors. NanoSPECT/CT imaging of the mice was performed 48 h and 72 h after injecting with 111 Indium ( 111 In) labeled PEG-HVGGSSV or PEG-control peptide. SPECT imaging revealed that 111 In-PEG-HVGGSSV specifically bound to cervical, esophageal, pancreatic, lung and brain tumors. Post SPECT biodistribution data further validated tumor-specific binding. Overall, HVGGSSV peptide specifically binds to the major groove of the TIP1 protein surface. PEGylated-HVGGSSV could be used to target cancers that overexpress TIP1.
KW - Molecular imaging
KW - Peptide
KW - SPECT imaging
KW - TIP1
UR - http://www.scopus.com/inward/record.url?scp=85061823835&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2019.02.008
DO - 10.1016/j.jconrel.2019.02.008
M3 - Article
C2 - 30763622
AN - SCOPUS:85061823835
VL - 298
SP - 194
EP - 201
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -