Nesligül ŞENTÜRK, Ayben TOP

PEG-peptide conjugate containing cathepsin B degradation unit as a doxorubicin carrier system

A drug delivery system (DDS) containing a cathepsin B degradable sequence and pH-responsive histidines was prepared by methoxypolyethylene glycol and peptide conjugation. Doxorubicin was attached to the carrier system using amide linkage to give the final form of the DDS, denoted as mPEG-AT3-DOX. mPEG-AT3-DOX exhibited a bimodal size distribution at about 15 and 30 nm independent of pH, whereas the size of the control DDS containing no peptide sequence, mPEG-DOX, was measured as ∼ 15–20 nm. At the end of 72 h, % doxorubicin release from both of the DDSs was observed to be below 8.5 ± 3% in the absence of cathepsin B, and it increased to 17 ± 2% in the presence of cathepsin B for mPEG-AT3-DOX. Complete degradation of AT3 peptide within 3 h upon incubation with cathepsin B suggests that lower than expected doxorubicin release is likely due to the aggregation tendency of mPEG-AT3-DOX. Absolute IC50 values indicated that the cytotoxicity trend of the samples is in the order of free DOX ≥ mPEG-AT3-DOX >mPEG-DOX. Considering these results, PEG-peptide-doxorubicin conjugates can be promising candidates in cancer therapy if they are designed to have more pronounced pH-responsive behavior to increase the drug release rate.

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