Tetrahedral DNA Nanostructures\nas Multifunctional\nDrug-Delivery Vehicles for Treating Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is the most prevalent\ntype of\nlung cancer, characterized by a relatively slow growth rate and a\npropensity toward distant metastases following local spread. These\nfactors present significant challenges in both diagnosis and treatment\nof NSCLC, particularly for early stage NSCLC. In this study, based\non the self-assembled functionalized tetrahedral DNA nanostructure\n(TDN), a multifunctional drug delivery system has been constructed\nfor NSCLC adenocarcinoma cell line A549 (A549 cells) to achieve intracellular\nimaging and combined drug delivery. The TDN was self-assembled <i>in vitro</i> and the four vertices of TDN were functionalized\nwith Cy5, s6 aptamer, p28 cell-penetrating peptide and siRNA, respectively.\nSubsequently, daunorubicin (DAU) was loaded to TDN to obtain DAU@TDN-p28-s6-siRNA\nthrough the intercalation in double-stranded DNA. While Cy5 is employed\nfor intracellular tracking and imaging, s6 aptamer is used to target\nA549 cells and enrich TDN around the cells, and p28 cell-penetrating\npeptide can facilitate the entrance of TDN into the cells via endocytosis.\nOnce DAU@TDN-p28-s6-siRNA is taken inside the cell, the modified siRNA\ncan bind to the mRNA guiding the translation of ERBB3 protein and\ndown-regulate its expression, ultimately leading to the inhibition\nof cell growth. Simultaneously, through the targeted delivery, DAU\naccurately inhibits the tumor cell activity, and thus achieving the\nsynergy with siRNA to inhibit the growth of tumor cells. <i>In\nvitro</i> experiments have demonstrated that compared to the\ncontrol, DAU@TDN-p28-s6-siRNA reduces the expression of ERBB3 protein\nby 71.27%, and reduces the viability of the target cell to 37.84%,\nas well as exhibits high targeting specificity. Therefore, the development\nof TDN assemblies provides an efficient way for diagnosis and treatment\nof tumor cells and has potential in the biomedical field.