Tumor-microenvironmental-response Bi-functional molecules for efficient imaging and anti-tumor activity therapy

Eur J Med Chem. 2022 Feb 15:230:114120. doi: 10.1016/j.ejmech.2022.114120. Epub 2022 Jan 12.

Abstract

To improve the visualization and potency of anticancer agents, the diagnosis and treatment integration bi-functional molecules were constructed based on active candidate BD7, approved drug Linifanib, and monoclonal antibody Bevacizumab. Commercial available Rhodamine B was inducted to realize imaging-aided diagnosis and target efficiency monitoring for cancer cells. In order to maintain the anticancer activity of drugs, disulfide bond was incorporated as releasable group based on tumor microenviroment. After design, synthesis and structure characterization of title compounds, various biological evaluation and cancer cell imaging analysis were carried out. The results indicated that these title diagnosis and treatment integration bi-functional molecules exhibited comparable potency with that of corresponding parent drug. Meanwhile, these agents afforded good performance in cell imaging and could be used to differentiate cancer cells from normal ovarian cells in real time. Further optimization of these bi-functional molecules is ongoing to improve the potency and precision and will be reported in due course. Our findings are expected to achieve efficient screening and real-time prognostic monitoring under the premise of high anti-tumor activity for clinical application.

Keywords: Anticancer agents; Bifunctional molecule; Cell imaging; Diagnosis and treatment integration; Releasable linker.

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Humans
  • Neoplasms* / diagnostic imaging
  • Neoplasms* / drug therapy

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents