Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome.

Abstract

Photodynamic therapy (PDT) is a promising alternative therapy that could be used as an adjunct to chemotherapy and surgery for cancer, and works by destroying tissue with visible light in the presence of a photosensitizer (PS) and oxygen. The PS should restrict tissue destruction only to the tumor and be activated by light of a specific wavelength; both of these properties are required. Arginine-rich peptides, such as cell-penetrating peptides, have membrane-translocating and nuclear-localizing activities, which have led to their application in various drug delivery modalities. Protamine (Pro) is an arginine-rich peptide with membrane-translocating and nuclear-localizing properties. The reaction of an N-hydroxysuccinimide (NHS) ester of rhodamine (Rho) and clinical Pro was carried out in this study to yield RhoPro, and a demonstration of its phototoxicity, wherein clinical Pro improved the effect of PDT, was performed. The reaction between Pro and the NHS ester of Rho is a solution-phase reaction that results in the complete modification of the Pro peptides, which feature a single reactive amine at the N-terminal proline and a single carboxyl group at the C-terminal arginine. This study aimed to identify a new type of PS for PDT by in vitro and in vivo experiments and to assess the antitumor effects of PDT, using the Pro-conjugated PS, on a cancer cell line. Photodynamic cell death studies showed that the RhoPro produced has more efficient photodynamic activities than Rho alone, causing rapid light-induced cell death. The attachment of clinical Pro to Rho, yielding RhoPro, confers the membrane-internalizing activity of its arginine-rich content on the fluorochrome Rho and can induce rapid photodynamic cell death, presumably owing to light-induced cell membrane rupture. PDT using RhoPro for HT-29 cells was very effective and these findings suggest that RhoPro is a suitable candidate as a PS for solid tumors.

• Authors: Chul-Kyu Park, Yong Ho Kim, Suhyun Hwangbo, Hoonsung Cho
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 12 Pg. 8185-8196 ( 2017) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 29184407 (Publication Type: Journal Article)

Chemical References

• Cell-Penetrating Peptides
• Fluorescent Dyes
• Photosensitizing Agents
• Protamines
• Rhodamines
• Succinimides
• N-hydroxysuccinimide

Topics

• Animals
• Cell Line, Tumor
• Cell-Penetrating Peptides (chemistry)
• Drug Delivery Systems (methods)
• Endocytosis (drug effects)
• Female
• Fluorescent Dyes (chemistry)
• HT29 Cells
• Humans
• Light
• Mice, Nude
• Photochemotherapy (methods)
• Photosensitizing Agents (chemistry, pharmacology)
• Protamines (chemistry, pharmacology)
• Rhodamines (chemistry)
• Succinimides (chemistry)
• Xenograft Model Antitumor Assays