Targeting ovarian solid tumors by pH triggered thermosensitive peptide-doxorubicin conjugate

Abstract

All anticancer drugs have undesirable side effects and lack target specificity. Drug delivery systems (DDS) developed so far have shown only limited success. Newer DDS with target specificity and undesirable side effects are, therefore, essential today. Given that sensitive polymers, peptides, dendrimers and hydrogels have been widely investigated as carriers for controlled release and target specificity, it is still a challenge to overcome the cumbersome problems faced in cancer treatment. In this context, we designed, synthesized and evaluated a high molecular weight, temperature and pH sensitive peptide (VPGVGVPGVG). Doxorubicin (Dox) was conjugated to the peptide using hydrazone linkage. The successful synthesis and conjugation of Dox was confirmed by FTIR, NMR and LCMS/MS studies. Isoelectric point calculator, UV-Spec, DSC, in vitro drug release studies revealed the thermosensitive and pH sensitive nature of the peptide. In vitro cytotoxic studies in SKOV-3 cell lines showed an IC50 value of 232.96 μg/ml for the dual sensitive peptide (DSP) compared to an IC50 value of 46.78 μg/ml for the dual sensitive peptide-Dox conjugate (DSP-DC) and 38.49 μg/ml for the free drug, Dox. In vivo fluorescence image analysis and histopathology studies revealed the site-specific capability of the DSP-DC.