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Molecules 2019, 24(4), 676; https://doi.org/10.3390/molecules24040676

The Limitations of Collagen/CPP Hybrid Peptides as Carriers for Cancer Drugs to FaDu Cells

Department of Chemistry and Biochemistry, California State University, Long Beach, 1250 Bellflower Blvd, Long Beach, CA 90840, USA
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Academic Editor: Wojciech Kamysz
Received: 30 December 2018 / Revised: 7 February 2019 / Accepted: 12 February 2019 / Published: 14 February 2019
(This article belongs to the Special Issue Peptide Chemistry Ⅱ)
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Abstract

The in vitro efficacy of cancer prodrugs varies significantly between malignant cell lines. The most commonly identified problems relate to delivery: uptake mechanism, endosomal entrapment, and drug release. Here we present the study of collagen/cell penetrating hybrid (COL/CPP) peptide carriers intended to deliver paclitaxel to the hypopharyngeal carcinoma (FaDu) cells. Confocal microscopy imaging revealed the surprising response of FaDu cell to COL/CPP in comparison to previously studied cancer cell lines: hybrid peptides that carry both COL and CPP domain adsorb on the FaDu cell surface. While the CPP domain was design to facilitate the cellular uptake, in the case of FaDu cells, it also induced detrimental interactions with the cell membrane. Despite surface adsorption, the colocalization study with endosomal markers EEA1 and LAMP1 reveals that COL/CPP is internalized via endosomal pathway, peptides are able to escape before lysosome formation and release paclitaxel. Therefore, the main obstacle for paclitaxel delivery to FaDu cells appears to be related to cell surface properties. This behavior seems specific to FaDu cells, and could be linked to previously reported overexpression of T5, heparanase splice variants that produces protein lacking enzymatic activity of heparanase. This results in increased concentration of HSPG on FaDu cell surface, and possibly creates a barrier for cellular uptake of highly charged COL/CPP. View Full-Text
Keywords: collagen peptides; cell penetrating peptides; hybrid peptides; FaDu; drug delivery; cell surface; HSPG collagen peptides; cell penetrating peptides; hybrid peptides; FaDu; drug delivery; cell surface; HSPG
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Ho, K.; Morfin, C.; Slowinska, K. The Limitations of Collagen/CPP Hybrid Peptides as Carriers for Cancer Drugs to FaDu Cells. Molecules 2019, 24, 676.

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