Intracellular
pH-Sensitive Metallo-Supramolecular Nanogels for Anticancer Drug Delivery
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Abstract
For
drug delivery systems, the most important factors are biocompatibility
and stability. To achieve excellent biocompatibility, learning from
naturally occurring systems may be the best choice. Herein, a series
of pH-sensitive metallo-supramolecular nanogels (MSNs) were prepared
by the metallo-supramolecular coordinated interaction between histidine
and iron-<i>meso</i>-tetraphenylporphin, which mimicks the
way that hemoglobin carries oxygen. With the excellent biocompatibility
and special supramolecular pH sensitivity, MSNs had been exploited
to load and release anticancer drug doxorubicin (DOX). In vitro drug
release profiles showed that only a small amount of the loaded DOX
was released in PBS solution at pH 7.4, while up to about 80% of the
loaded DOX could be quickly released at pH 5.3 due to the pH-dependent
disassembly of MSNs. Confocal laser scanning microscopy (CLSM) and
flow cytometry were used to verify the cellular uptake and intracellular
drug release behaviors of DOX-loaded MSNs toward MCF-7. Efficient
cellular proliferation inhibition against MCF-7 and HeLa cells was
also observed by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium
bromide (MTT) assay. These features suggested that MSNs could be of
great potential as intelligent drug delivery systems