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Tracking intracellular nuclear targeted-chemotherapy of chidamide-loaded Prussian blue nanocarriers by SERS mapping
Xinyue Xing1, Wanqing Zhong1, Ping Tang2
1Guangdong Provincial Key Laboratory of Nanophotonic Functional Materials and Devices, South China Normal University, Guangzhou, China.
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 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.
Insights
This study introduces a novel Prussian blue nanocarrier for targeted delivery of chidamide (CHI), improving its efficacy against lymphoblastic leukemia by enhancing cellular uptake and reducing side effects.
Area of Science:
- Nanotechnology
- Epigenetics
- Cancer Therapy
Background:
- Chidamide (CHI), a histone deacetylase inhibitor, regulates oncogenic gene expression epigenetically.
- CHI faces limitations including off-target effects, poor cellular accumulation, and inefficient nuclear entry, hindering its therapeutic potential.
- Dual-targeted nanodrug delivery systems offer a promising strategy to overcome these limitations.
Purpose of the Study:
- To develop a novel Prussian blue (PB)-based nanocarrier system for targeted delivery of chidamide (CHI).
- To integrate surface-enhanced Raman scattering (SERS) for intracellular tracking of CHI.
- To enhance cancer cell and nuclear targeting for improved chemotherapy in lymphoblastic leukemia.
Main Methods:
- Fabrication of CHI-loaded PB nanocarriers with dual-targeting capabilities.
- Utilizing SERS for background-free intracellular tracking and localization of CHI.
- In vitro cytotoxicity assays on Jurkat cells.
- SERS spectral analysis to identify apoptotic markers.
Main Results:
- The developed CHI-loaded PB nanocarriers demonstrated significant inhibition of Jurkat cell proliferation.
- SERS analysis confirmed intracellular CHI localization and revealed markers of cellular apoptosis, including DNA fragmentation and histone acetylation.
- The targeted nanocarrier system enhanced cellular internalization and chemotherapeutic effects.
Conclusions:
- The CHI-loaded PB nanocarrier system effectively targets cancer cells and nuclei, improving therapeutic efficacy.
- SERS mapping provides a valuable tool for tracking nanodrugs intracellularly.
- This nanocarrier system offers a novel approach for targeted lymphoblastic leukemia chemotherapy.
