Deformable Smart DNA Nanomachine for Synergistic Intracellular Cancer‐Related miRNAs Imaging and Chemo‐Gene Therapy of Drug‐Resistant Tumors

Abstract

Diagnosis and treatment of tumor especially drug‐resistant tumor remains a huge challenge, which requires intelligent nanomedicines with low toxic side effects and high efficacy. Herein, deformable smart DNA nanomachines are developed for synergistic intracellular cancer‐related miRNAs imaging and chemo‐gene therapy of drug‐resistant tumors. The tetrahedral DNA framework (MA‐TDNA) with fluorescence quenched component and five antennas is self‐assembled first, and then DOX molecules are loaded on the MA‐TDNAs followed by linking MUC1‐aptamer and Mcl‐1 siRNA to the antennas of MA‐TDNA, so that the apt‐MA‐TDNA@DOX‐siRNA (DNA nanomachines) is constructed. The DNA nanomachine can respond to two tumor‐related miRNAs in vitro and in vivo, which can undergo intelligent miRNA‐triggered opening of the framework, resulting in the “turn on” of the fluorescence for sensitively and specifically sensing intracellular miRNAs. Meanwhile, both miRNA‐responded rapid release and pH‐responded release of DOX are achieved for chemotherapy of tumor. In addition, the gene therapy of the DNA nanomachines is achieved due to the miRNA‐specific capture and the RNase H triggered release of Mcl‐1 siRNA. The DNA nanomachines intergrading both tumor imaging and chemo‐gene therapy in single nanostructures realized efficient tumor‐targeted, image‐guided, and microenvironment‐responsive tumor diagnosis and treatment, which provides a synergetic antitumor effect on drug‐resistant tumor.

Protease-Responsive Bitext Editing Biopolymer for Breast Cancer Imaging In Vivo

“…The first one is MUC1-DNF (mDNF) generated by RCA from a template embedded with the MUC1 aptamer and a peptide binding site. The MUC1 is a transmembrane oncogenic protein that plays a significant role in malignant transformation and disease evolution, including cell proliferation, survival, self-renewal, and metastatic invasion. , Thus, the cancer cells overexpressed with MUC1 would be successfully recognized by the mDNF with the help of MUC1 aptamer. , The second domain is a peptide-loaded DNA binder that consists of a DNA sequence complementary to the binding site and a peptide substrate probe that is impregnated with FAM (green fluorescent group) at one end and DABCYL (quenching group) at the other end. After the successful assembly of ppDNF, it is administered to the mice via tail vein injection where ppDNF has been actively enriched to the target site by aptamer, and the peptide substrates accumulated in ppDNF are cleaved by CatB that is specifically overexpressed in breast cancer cells.…”

“…34,35 Thus, the cancer cells overexpressed with MUC1 would be successfully recognized by the mDNF with the help of MUC1 aptamer. 36,37 The second domain is a peptide-loaded DNA binder that consists of a DNA sequence complementary to the binding site and a peptide substrate probe that is impregnated with FAM (green fluorescent group) at one end and DABCYL (quenching group) at the other end. After the successful assembly of ppDNF, it is administered to the mice via tail vein injection where ppDNF has been actively enriched to the target site by aptamer, and the peptide substrates accumulated in ppDNF are cleaved by CatB that is specifically overexpressed in breast cancer cells.…”