Tracking intracellular nuclear targeted-chemotherapy of chidamide-loaded Prussian blue nanocarriers by SERS mapping

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 nanosystem 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.