Here we report the design and synthesis of two new peptide-Dox conjugates (1 and 2) for the specific delivery of Dox to the breast cancer cells and the ability to overcome P-glycoprotein multidrug resistance pathway in both drug-sensitive and drug-resistant cancer cells. Peptide-Dox conjugates were evaluated for DOX release in human serum, intracellular delivery compared to free Dox in three cancerous cells (MCF-7, MDA-MB-435, and MDA-MB-435-MDR) and two noncancerous cell lines (HUVEC and MCF-10A), and cytotoxicity compared to free Dox. Results show that both the peptide-Dox conjugates (1 and 2) enter sensitive and resistant cell lines with minimal uptake in normal cells compared to free Dox. Cellular uptake is most likely mediated by a cell specific receptor, as the amount of internalized conjugates significantly decreased in the presence of excess free peptide. Importantly, conjugate 1 is equally cytotoxic as Dox in drug sensitive breast cancer cells and 4 times more potent than free Dox in Dox resistant cell line. Overall, the peptide-Dox ester conjugate 1 showed better breast targeting efficacy than the amide conjugate 2, most likely due to the slow release of Dox from the stable amide linkage.

Here we report the design and synthesis of two new peptide-Dox conjugates (1 and 2) for the specific delivery of Dox to the breast cancer cells and the ability to overcome P-glycoprotein multidrug resistance pathway in both drug-sensitive and drug-resistant cancer cells. Peptide-Dox conjugates were evaluated for DOX release in human serum, intracellular delivery compared to free Dox in three cancerous cells (MCF-7, MDA-MB-435, and MDA-MB-435-MDR) and two noncancerous cell lines (HUVEC and MCF-10A), and cytotoxicity compared to free Dox. Results show that both the peptide-Dox conjugates (1 and 2) enter sensitive and resistant cell lines with minimal uptake in normal cells compared to free Dox. Cellular uptake is most likely mediated by a cell specific receptor, as the amount of internalized conjugates significantly decreased in the presence of excess free peptide. Importantly, conjugate 1 is equally cytotoxic as Dox in drug sensitive breast cancer cells and 4 times more potent than free Dox in Dox resistant cell line. Overall, the peptide-Dox ester conjugate 1 showed better breast targeting efficacy than the amide conjugate 2, most likely due to the slow release of Dox from the stable amide linkage.

Here we report the design and synthesis of two new peptide-Dox conjugates (1 and 2) for the specific delivery of Dox to the breast cancer cells and the ability to overcome P-glycoprotein multidrug resistance pathway in both drug-sensitive and drug-resistant cancer cells. Peptide-Dox conjugates were evaluated for DOX release in human serum, intracellular delivery compared to free Dox in three cancerous cells (MCF-7, MDA-MB-435, and MDA-MB-435-MDR) and two noncancerous cell lines (HUVEC and MCF-10A), and cytotoxicity compared to free Dox. Results show that both the peptide-Dox conjugates (1 and 2) enter sensitive and resistant cell lines with minimal uptake in normal cells compared to free Dox. Cellular uptake is most likely mediated by a cell specific receptor, as the amount of internalized conjugates significantly decreased in the presence of excess free peptide. Importantly, conjugate 1 is equally cytotoxic as Dox in drug sensitive breast cancer cells and 4 times more potent than free Dox in Dox resistant cell line. Overall, the peptide-Dox ester conjugate 1 showed better breast targeting efficacy than the amide conjugate 2, most likely due to the slow release of Dox from the stable amide linkage.

Here we report the design and synthesis of two new peptide-Dox conjugates (1 and 2) for the specific delivery of Dox to the breast cancer cells and the ability to overcome P-glycoprotein multidrug resistance pathway in both drug-sensitive and drug-resistant cancer cells. Peptide-Dox conjugates were evaluated for DOX release in human serum, intracellular delivery compared to free Dox in three cancerous cells (MCF-7, MDA-MB-435, and MDA-MB-435-MDR) and two noncancerous cell lines (HUVEC and MCF-10A), and cytotoxicity compared to free Dox. Results show that both the peptide-Dox conjugates (1 and 2) enter sensitive and resistant cell lines with minimal uptake in normal cells compared to free Dox. Cellular uptake is most likely mediated by a cell specific receptor, as the amount of internalized conjugates significantly decreased in the presence of excess free peptide. Importantly, conjugate 1 is equally cytotoxic as Dox in drug sensitive breast cancer cells and 4 times more potent than free Dox in Dox resistant cell line. Overall, the peptide-Dox ester conjugate 1 showed better breast targeting efficacy than the amide conjugate 2, most likely due to the slow release of Dox from the stable amide linkage.

Here we report the design and synthesis of two new peptide-Dox conjugates (1 and 2) for the specific delivery of Dox to the breast cancer cells and the ability to overcome P-glycoprotein multidrug resistance pathway in both drug-sensitive and drug-resistant cancer cells. Peptide-Dox conjugates were evaluated for DOX release in human serum, intracellular delivery compared to free Dox in three cancerous cells (MCF-7, MDA-MB-435, and MDA-MB-435-MDR) and two noncancerous cell lines (HUVEC and MCF-10A), and cytotoxicity compared to free Dox. Results show that both the peptide-Dox conjugates (1 and 2) enter sensitive and resistant cell lines with minimal uptake in normal cells compared to free Dox. Cellular uptake is most likely mediated by a cell specific receptor, as the amount of internalized conjugates significantly decreased in the presence of excess free peptide. Importantly, conjugate 1 is equally cytotoxic as Dox in drug sensitive breast cancer cells and 4 times more potent than free Dox in Dox resistant cell line. Overall, the peptide-Dox ester conjugate 1 showed better breast targeting efficacy than the amide conjugate 2, most likely due to the slow release of Dox from the stable amide linkage.