Effective Renal Clearance and Photothermal Therapy of a Cyclodextrin-Modified Quaterrylene Derivative

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Abstract
Metabolic clearance of drugs from the body is a very key element for future clinical applications. Compared with the liver-bile metabolic route, the renal-urinary route is the most desirable and efficient clearance pathway for practical use in clinical trials and can effectively decrease the long-term risks of unpredictable intracellular catabolism and the potential toxicity to normal organs. However, renal-clearable photothermal therapy (PTT) agents were limited. In this paper, a permethyl-β-cyclodextrin-modified quaterrylene bisimide derivative (QDI-CD) was developed. QDI-CD as a biocompatible molecule could effectively be cleared with the renal clearance efficiency of (67.00±2.37) % at 24 h by the renal-urinary route when administered by tail vein injection. Importantly, the structure of QDI-CD in urine after metabolism does not change. Furthermore, QDI-CD was as a potent photoacoustic and photothermal agent, could effectively enriched in tumor tissue after four hours post-injection, and showed the effective photothermal therapy in mice. This work developed a potent organic PTT agent with good renal clearance from the body and with promise for future clinical applications.
Funding Information
  • National Natural Science Foundation of China (21372059, 21572044)
  • the Priority Strategy Project of Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education (ts2019002)
  • the Foundation of the Department of Science and Technology of Hebei Province (19241303D)

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