Theranostic Polyaminocarboxylate-Cyanine-Transferrin Conjugate for Anticancer Therapy and Near-Infrared Optical Imaging.
Iron chelation therapy has been recognized as a promising antitumor therapeutic strategy. Herein we report a novel theranostic agent for targeted iron chelation therapy and near-infrared (NIR) optical imaging of cancers. The theranostic agent was prepared by incorporation of a polyaminocarboxylate-based cytotoxic chelating agent (N-NE3TA; 7-[2-[(carboxymethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) and a NIR fluorescent cyanine dye (Cy5.5) onto a tumor-targeting transferrin (Tf). The N-NE3TA-Tf conjugate (without Cy5.5) was characterized and evaluated for antiproliferative activity in HeLa, HT29, and PC3 cancer cells, which have elevated expression levels of the transferrin receptor (TfR). The N-NE3TA-Tf conjugate displayed significant inhibitory activity against all three cancer cell lines. The NIR dye Cy5.5 was then incorporated into N-NE3TA-Tf, and the resulting cytotoxic and fluorescent transferrin conjugate N-NE3TA-Tf-Cy5.5 was shown by microscopy to enter TfR-overexpressing cancer cells. This theranostic conjugate has potential application for dual use in targeted iron chelation cancer therapy and NIR fluorescence imaging.
Department of Chemistry, College of Science, Illinois Institute of Technology, 3101 S. Dearborn St., LS 182, Chicago, IL, 60616, USA.
Chi Soo
CS
Kang
Department of Chemistry, College of Science, Illinois Institute of Technology, 3101 S. Dearborn St., LS 182, Chicago, IL, 60616, USA.
Siyuan
S
Ren
Department of Chemistry, College of Science, Illinois Institute of Technology, 3101 S. Dearborn St., LS 182, Chicago, IL, 60616, USA.
Xiang
X
Sun
Department of Chemistry, College of Science, Illinois Institute of Technology, 3101 S. Dearborn St., LS 182, Chicago, IL, 60616, USA. Chong@iit.edu.
Hyun-Soon
HS
Chong
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002232:Carbocyanines / Q000737:chemistry* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D061848:Optical Imaging / Q000379:methods*; D011073:Polyamines / Q000737:chemistry* / Q000494:pharmacology; D019265:Spectroscopy, Near-Infrared; D013329:Structure-Activity Relationship; D014168:Transferrin / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D002264:Carboxylic Acids; D002614:Chelating Agents; D011073:Polyamines; D014168:Transferrin
anticancer therapy; fluorescent probes; optical imaging; theranostic agents; transferrin conjugates