Development of Iodinated Indocyanine Green Analogs as a Strategy for Targeted Therapy of Liver Cancer.
Sierra C MarkerAndres F EspinozaA Paden KingSarah E WoodfieldRoma H PatelKwamena BaidooMeredith N NixLarissa Miasiro CiaramicoliYoung Tae ChangFreddy E EscorciaSanjeev A VasudevanMartin J SchnermannPublished in: ACS medicinal chemistry letters (2023)
Liver cancer is one of the leading causes of cancer-related deaths, with a significant increase in incidence worldwide. Novel therapies are needed to address this unmet clinical need. Indocyanine green (ICG) is a broadly used fluorescence-guided surgery (FGS) agent for liver tumor resection and has significant potential for conversion to a targeted therapy. Here, we report the design, synthesis, and investigation of a series of iodinated ICG analogs (I-ICG), which can be used to develop ICG-based targeted radiopharmaceutical therapy. We applied a CRISPR-based screen to identify the solute carrier transporter, OATP1B3, as a likely mechanism for ICG uptake. Our lead I-ICG compound specifically localizes to tumors in mice bearing liver cancer xenografts. This study introduces the chemistry needed to incorporate iodine onto the ICG scaffold and defines the impact of these modifications on key properties, including targeting liver cancer in vitro and in vivo .
Keyphrases
- fluorescence imaging
- photodynamic therapy
- gene expression
- crispr cas
- risk factors
- high throughput
- stem cells
- coronary artery disease
- magnetic resonance imaging
- cancer therapy
- magnetic resonance
- metabolic syndrome
- drug delivery
- climate change
- single cell
- type diabetes
- mesenchymal stem cells
- coronary artery bypass
- bone marrow
- tissue engineering
- quantum dots
- drug discovery