Tracking intracellular nuclear targeted-chemotherapy of chidamide-loaded Prussian blue nanocarriers by SERS mapping
COLLOIDS AND SURFACES B-BIOINTERFACES(2023)
Abstract
The novel histone deacetylase drug chidamide (CHI) has been proven to regulate gene expression associated with oncogenesis via epigenetic mechanisms. However, huge side effects such as non-targeting, poor intracellular accumulation and low nuclear entry efficiency severely restrict its therapeutic efficacy. Dual-targeted nanodrug delivery systems have been proposed as the solution. Herein, we developed a CHI-loaded drug delivery nano-system based on Prussian blue (PB) nanocarrier, which combines surface-enhanced Raman scattering (SERS) tracking function with cancer cell/nuclear-targeted chemotherapy capability. With the property of background-free SERS mapping, PB nanocarriers can serve as tracking agents to localize intracellular CHI. The incorporation of targeted molecules specifically enhances the cancer cell/nuclear internalization and chemotherapeutic effects of CHI-loaded PB nanocarriers. In vitro cytotoxicity assay clearly shows that the constructed CHI-loaded PB nanocarriers have significant inhibitory on Jurkat cell proliferation. Furthermore, SERS spectral analysis of Jurkat cells incubated with the CHI-loaded PB nanocarriers reveals obvious features of cellular apoptosis: DNA skeleton fragmentation, chromatin depolymerization, histone acetylation, and nucleosome conformation change. Importantly, this CHI-loaded PB nanocarrier will provide a new insight for lymphoblastic leukemia targeted chemotherapy.
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Key words
Chidamide,Prussian blue nanocarriers,Nuclear-targeted chemotherapy,SERS tracking
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