A small subset of heptamethine dyes (cyanine-7 or Cy7) share an intriguing characteristic: preferential tumor accumulation and retention. These dyes absorb in the near-infrared (NIR) region (above 750 nm) and perform active targeting to deliver therapeutic and toxic cargoes to various tumor models in vivo. In this work, four heptamethines 1 were synthesized, which have a gemcitabine fragment attached to the meso-position of the Cy7 core. Theranostic agent 1a was discovered that localized in glioblastoma tumor cells, has absorption maxima in NIR region, and showed similar therapeutic effect to gemcitabine but at one-third the molar dose.
We hypothesized that conjugation of the near‐infrared dye MHI‐148 with the anti‐leukemia drug dasatinib might produce a potential theranostic for glioblastoma. In fact, the conjugate was found to bind the kinases Src and Lyn, and to inhibit the viability of a glioblastoma cell line with significantly greater potency than dasatinib alone, MHI‐148 alone, or a mixture of dasatinib and MHI‐148 at the same concentration. It was also used to successfully image a subcutaneous glioblastoma tumor in vivo.
This study was undertaken to target cell surface receptors other than the ones typically associated with breast cancer {estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)}. It was also launched to use small molecules other than those most widely used for active targeting in general ( e.g. folate and carbonic anhydrase IX ligands). Specifically, the focus of this study was on unique small molecules that bind the TrkC receptor, which is overexpressed in metastatic breast cancer. A conjugate (1) of a TrkC-targeting small molecule and the highly cytotoxic warhead, DM4 (a maytansinoid), was prepared. Cellular studies featuring TrkC and TrkC human breast cells indicated this conjugate might have a better therapeutic effect than DM4 alone. It emerged that the conjugate 1 was very efficacious in vivo, completely ablating orthotopic 4T1 breast tumor in one case and dramatically reducing the tumor size in four other mice. Throughout, no significant weight loss or obvious neurotoxic effects were observed in the animals tested.
We present several critical design criteria of minimalist peptidomimetics deduced via extensive computational and data-mining studies on nine representative mimic designs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.