Conjugate of Doxorubicin to Albumin-Binding Peptide Outperforms Aldoxorubicin.

ABSTRACT: Short circulation time and off-target toxicity are the main challenges faced by small-molecule chemotherapeutics. To overcome these shortcomings, an albumin-binding peptide conjugate of chemotherapeutics is developed that binds specifically to endogenous albumin and harnesses its favorable pharmacokinetics and pharmacodynamics for drug delivery to tumors. A protein-G-derived albumin-binding domain (ABD) is conjugated with doxorubicin (Dox) via a pH-sensitive linker. One to two Dox molecules are conjugated to ABD without loss of aqueous solubility. The albumin-binding ABD-Dox conjugate exhibits nanomolar affinity for human and mouse albumin, and upon administration in mice, shows a plasma half-life of 29.4 h, which is close to that of mouse albumin. Additionally, 2 h after administration, A

SUBMITTER: Yousefpour P 

PROVIDER: S-EPMC8114561 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature