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Development Of Novel Peptide-Doxorubicin Conjugates For Targeting Triple-Negative Breast Cancer, Azam Saghaeidehkordi
Development Of Novel Peptide-Doxorubicin Conjugates For Targeting Triple-Negative Breast Cancer, Azam Saghaeidehkordi
Pharmaceutical Sciences (PhD) Dissertations
Triple-negative breast cancer (TNBC) is the most aggressive and difficult to treat subtype of breast cancer. Chemotherapy is an active treatment option in combination with other treatments; however, the side effects limit the effective therapeutic dose. To selectively target the cancer cells, I have synthesized three peptide-drug conjugates (PDCs) to specifically target the TNBC cells. The first PDC contains peptide 18-4 with an additional cysteine in the N-terminal (NH2- CWxEAAYQrFL-CONH2) linked to aldoxorubicin (Aldox), a modified version of a common chemotherapy drug doxorubicin (Dox). The cytotoxicity of the PDC and free Dox (positive control) were assessed against MDA-MB-231, MDA-MB-468, and …
Design, Synthesis, And Evaluation Of A Novel Cytotoxic Peptide-Doxorubicin Conjugate Targeting Triple-Negative Breast Cancer, Elmira Ziaei
Design, Synthesis, And Evaluation Of A Novel Cytotoxic Peptide-Doxorubicin Conjugate Targeting Triple-Negative Breast Cancer, Elmira Ziaei
Pharmaceutical Sciences (PhD) Dissertations
The aim of this thesis was to design, synthesize, and characterize a novel peptide-doxorubicin conjugate, evaluate in vitro stability and cytotoxicity properties of the conjugate and study its mechanism for uptake into the triple-negative breast cancer (TNBC) cells. For the synthesis of the conjugate, first, doxorubicin (Dox) was conjugated to a highly efficient established cross-linker, MCC, to give an intermediate product, MCC-Dox. MCC-Dox was characterized using NMR spectroscopy, mass spectrometry, and RP-HPLC and purified for subsequent reaction. Second, the 11-mer peptide 18-4 (NH2-CWxEAAYQrFL-CONH2) with high proteolytic stability and specificity for breast cancer cells was reacted with …