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.