Back to Journals » International Journal of Nanomedicine » Volume 7

Poly(L-histidine)-tagged 5-aminolevulinic acid prodrugs: new photosensitizing precursors of protoporphyrin IX for photodynamic colon cancer therapy

Authors Johnson RP, Chung CW, Jeong YI, Kang DH, Suh H, Kim I

Received 29 December 2011

Accepted for publication 11 February 2012

Published 17 May 2012 Volume 2012:7 Pages 2497—2512

DOI https://doi.org/10.2147/IJN.S29582

Review by Single-blind

Peer reviewer comments 5

Renjith P Johnson,1* Chung-Wook Chung,2* Young-Il Jeong,2 Dae Hwan Kang,2 Hongsuk Suh,3 Il Kim,1

1WCU Centre for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan, 2National Research and Development Center for Hepatobiliary Cancer, Pusan National University, Yangsan Hospital, Yangsan, Gyeongnam, 3Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Pusan, Korea

*These authors contributed equally to this work

Background: 5-Aminolevulinic acid (ALA) and its derivatives have been widely used in photodynamic therapy. The main drawback associated with ALA-based photodynamic therapy (ALA-PDT) and ALA fluorescence diagnosis results from the hydrophilic nature of ALA and lack of selectivity for tumor versus nontumor cells. The application of certain triggers, such as pH, into conventional sensitizers for controllable 1O2 release is a promising strategy for tumor-targeted treatment.
Methods: A series of pH-sensitive ALA-poly(L-histidine) [p(L-His)n] prodrugs were synthesized via ring opening polymerization of 1-benzyl-N-carboxy-L-histidine anhydride initiated by the amine hydrochloride group of ALA itself. As an alternative to ALA for PDT, the synthesized prodrugs were used to treat a cultured human colon cancer HCT116 cell line under different pH conditions. The effect of ALA-p(L-His)n derivatives was evaluated by monitoring the fluorescence intensity of protoporphyrin IX, and measuring the cell survival rate after suitable light irradiation.
Results: The cytotoxicity and dark toxicity of ALA and synthesized ALA-p(L-His) derivatives in HEK293T and HCT116 cells in the absence of light at pH 7.4 and 6.8 shows that the cell viability was relatively higher than 100%. ALA-p(L-His)n showed high phototoxicity and selectivity in different pH conditions compared with ALA alone. Because the length of the histidine chain increases in the ALA-p(L-His)n prodrugs, the PDT effect was found to be more powerful. In particular, high phototoxicity was observed when the cells were treated with ALA-p(L-His)15, compared with treatment using ALA alone.
Conclusion: The newly synthesized ALA-p(L-His)n derivatives are an effective alternative to ALA for enhancing protoporphyrin IX production and the selectivity of the phototoxic effect in tumor cells.

Keywords: 5-aminolevulinic acid, photodynamic therapy, poly(L-histidine), bioconjugate, cancer cells

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier

Chaturvedi M, Molino Y, Sreedhar B, Khrestchatisky M, Kaczmarek L

International Journal of Nanomedicine 2014, 9:575-588

Published Date: 20 January 2014

Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4

Shiozaki Y, Kitajima T, Mazaki T, Yoshida A, Tanaka M, Umezawa A, Nakamura M, Yoshida Y, Ito Y, Ozaki T, Matsukawa A

International Journal of Nanomedicine 2013, 8:1349-1360

Published Date: 9 April 2013

Functionalization of immunostimulating complexes (ISCOMs) with lipid vinyl sulfones and their application in immunological techniques and therapy

Cruz-Bustos T, González-González G, Morales-Sanfrutos J, Megí­a-Fernández A, Santoyo-González F, Osuna A

International Journal of Nanomedicine 2012, 7:5941-5956

Published Date: 3 December 2012

Antibacterial hemostatic dressings with nanoporous bioglass containing silver

Hu G, Xiao L, Tong P, Bi D, Wang H, Ma H, Zhu G, Liu H

International Journal of Nanomedicine 2012, 7:2613-2620

Published Date: 28 May 2012

Zerovalent bismuth nanoparticles inhibit Streptococcus mutans growth and formation of biofilm

Hernandez-Delgadillo R, Velasco-Arias D, Diaz D, Arevalo-Niño K, Garza-Enriquez M, De la Garza-Ramos MA, Cabral-Romero C

International Journal of Nanomedicine 2012, 7:2109-2113

Published Date: 24 April 2012

Biscarbamate cross-linked polyethylenimine derivative with low molecular weight, low cytotoxicity, and high efficiency for gene delivery

Wang YQ, Su J, Wu F, Lu P, Yuan LF, Yuan WE, Sheng J, Jin T

International Journal of Nanomedicine 2012, 7:693-704

Published Date: 9 February 2012

Biomimetic component coating on 3D scaffolds using high bioactivity of mesoporous bioactive ceramics

Yun HS, Kim SH, Khang DW, Choi JI, Kim HH, Kang MJ

International Journal of Nanomedicine 2011, 6:2521-2531

Published Date: 21 October 2011

Nanovaccine for leishmaniasis: preparation of chitosan nanoparticles containing Leishmania superoxide dismutase and evaluation of its immunogenicity in BALB/c mice

Danesh-Bahreini MA, Shokri J, Samiei A, Kamali-Sarvestani E, Barzegar-Jalali M, Mohammadi-Samani S

International Journal of Nanomedicine 2011, 6:835-842

Published Date: 20 April 2011

Plant sterols as dietary adjuvants in the reduction of cardiovascular risk: theory and evidence

Craig S Patch, Linda C Tapsell, Peter G Williams, Michelle Gordon

Vascular Health and Risk Management 2006, 2:157-162

Published Date: 15 June 2006