pH-Responsive and Gemcitabine-Containing DNA Nanogel To Facilitate the Chemodrug Delivery.
Gaifang PanQuanbing MouYuan MaFei DingJiao ZhangYuanyuan GuoXiangang HuangQifeng LiXinyuan ZhuChuan ZhangPublished in: ACS applied materials & interfaces (2019)
Herein, we construct a structure-switchable gemcitabine (Ge)-containing DNA nanogel that can respond to the intracellular acidic environment, subsequently facilitating the chemodrug release inside the cells. Based on the structural similarity between Ge and deoxycytidine (dC), dC nucleotides in the component DNA strands used for nanogel assembly are fully replaced by Ge during their synthesis. By changing the designed sequences, two Ge-containing Y-shaped motifs with different sticky ends are first assembled and then associated together to form nanogel by sticky-end hybridizations. In particular, one of the sticky-end sequences is arbitrarily designed to be rich of Ge and the other is designed to be partially complementary to the first Ge-rich sticky end. At the neutral or basic condition, the Ge-rich sticky ends hybridize with the partially complementary sticky ends on the second Y motifs, keeping the assembled nanogel stable. Upon being exposed to the acidic condition, Ge-rich sticky ends intend to form intramolecular i-motif-like quadruplex structures, resulting in the disassembly of the nanogel. On the one hand, the nanosized feature enables the Ge-containing nanogel with rapid cellular uptake behavior. On the other hand, the pH-responsive feature endows the rapid disassembly of the nanogel to facilitate the enzymatic drug release inside the cell, resulting in the enhanced anticancer activity of the DNA-based drug delivery system.
Keyphrases
- circulating tumor
- cell free
- drug release
- single molecule
- machine learning
- dendritic cells
- stem cells
- drug delivery
- deep learning
- single cell
- high resolution
- mesenchymal stem cells
- signaling pathway
- hydrogen peroxide
- loop mediated isothermal amplification
- cell proliferation
- reactive oxygen species
- circulating tumor cells
- neural network
- genetic diversity