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Issue 18, 2018
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Hybrid nanoparticles based on chlorin e6-conjugated hyaluronic acid/poly(L-histidine) copolymer for theranostic application to tumors

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Abstract

The aim of this study is to synthesize multifunctional hybrid nanoparticles composed of hyaluronic acid (HA) and poly(L-histidine) (PHS) with a disulfide linkage and chlorin e6 (HAPHSce6ss) for diagnostic and therapeutic application against breast tumor cells. The reductive end of HA was conjugated with cystamine to make a disulfide linkage (HA–cystamine). PHS was conjugated with Ce6 with the aid of carbodiimide chemistry (PHS–ce6). Then, HA–cystamine was conjugated with the carboxyl group of Ce6 to make an HAPHSce6ss copolymer. Nanoparticles of HAPHSce6ss copolymer have small particle sizes of less than 100 nm and their diameters increased with acidic pH, indicating that HAPHSce6ss nanoparticles have pH-sensitivity. Furthermore, ce6 was activated in the acidic environment and had redox-status in a fluorescence study. In a cell culture study, the nanoparticles were specifically targeted at the CD44 receptor of MDA-MB231 cells while CD44-negative MCF7 cells had no CD44-specificity. The nanoparticles exhibited an enhanced association with cells and were more fluorescent at acidic pH or in the presence of GSH. They inhibited the growth of tumor cells in a CD44 receptor specific or pH-sensitive manner. In an in vivo animal tumor xenograft study using mice, HAPHSce6ss nanoparticles predominantly targeted an MDA-MB231 tumor rather than an MCF7 tumor and effectively inhibited tumor growth. HAPHSce6ss nanoparticles have CD44 specificity, pH/redox dual sensitivity and a fluorescence diagnostic function against tumor cells. We suggest that HAPHSce6ss nanoparticles are a promising candidate for theranostic application to tumors.

Graphical abstract: Hybrid nanoparticles based on chlorin e6-conjugated hyaluronic acid/poly(l-histidine) copolymer for theranostic application to tumors

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Publication details

The article was received on 27 Nov 2017, accepted on 08 Apr 2018 and first published on 11 Apr 2018


Article type: Paper
DOI: 10.1039/C7TB03068A
Citation: J. Mater. Chem. B, 2018,6, 2851-2859
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    Hybrid nanoparticles based on chlorin e6-conjugated hyaluronic acid/poly(L-histidine) copolymer for theranostic application to tumors

    S. Lee and Y. Jeong, J. Mater. Chem. B, 2018, 6, 2851
    DOI: 10.1039/C7TB03068A

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