biostudies-literatureAyalew LNational Institute of General Medical SciencesNIGMS NIH HHS814-819https://www.ebi.ac.uk/biostudies/studies/S-EPMC5554909biostudies-literatureUnknown8(8)Paclitaxel (PTX) is one of the most potent cancer drugs; however, its low solubility and strong systemic side effects limit its clinical applications. To overcome these issues, new drug formulations and chemical modifications have been proposed. In this study, we present conjugation of PTX to hybrid collagen-cell penetrating peptide (COL-CPP) carriers. The peptide carrier is highly soluble and utilizes a unique stabilization strategy: folding into a triple helix. Here, we report the formation of PTX-COL-CPP prodrug that has similar drug potency as free PTX when tested in Jurkat (human T lymphocyte of acute T cell leukemia) cells but not in A549 (human epithelial of lung carcinoma) cells. Confocal images and flow cytometry show that this behavior originates from lower cellular uptake of COL-CPP and endosomal entrapment of the prodrug in A549, but not in Jurkat cells.ACS medicinal chemistry lettersConjugation of Paclitaxel to Hybrid Peptide Carrier and Biological Evaluation in Jurkat and A549 Cancer Cell Lines.PMC5554909TL4 GM118980R25 GM071638SC3 GM099594GM099594Oh MAyalew LAcuna JUrfano SFMorfin CGamboa ASlowinska KSablan AfalseConjugation of Paclitaxel to Hybrid Peptide Carrier and Biological Evaluation in Jurkat and A549 Cancer Cell Lines.Paclitaxel (PTX) is one of the most potent cancer drugs; however, its low solubility and strong systemic side effects limit its clinical applications. To overcome these issues, new drug formulations and chemical modifications have been proposed. In this study, we present conjugation of PTX to hybrid collagen-cell penetrating peptide (COL-CPP) carriers. The peptide carrier is highly soluble and utilizes a unique stabilization strategy: folding into a triple helix. Here, we report the formation of PTX-COL-CPP prodrug that has similar drug potency as free PTX when tested in Jurkat (human T lymphocyte of acute T cell leukemia) cells but not in A549 (human epithelial of lung carcinoma) cells. Confocal images and flow cytometry show that this behavior originates from lower cellular uptake of COL-CPP and endosomal entrapment of the prodrug in A549, but not in Jurkat cells.2017-01-01T00:00:00Z2017 Aug2024-11-12T17:59:51.231Z2019-03-26T23:50:06ZS-EPMC55549092883579410.1021/acsmedchemlett.7b00117