In-vivo Polyvalent Aptamer@Protein-Based Nanocarrier with Synergistic Charge Effect for High Drug Loading, High Nuclease Resistance, and High Receptor Accessibility

Open AccessCCS ChemistryRESEARCH ARTICLES19 Jun 2024In-vivo Polyvalent Aptamer@Protein Based Nanocarrier with Synergistic Charge Effect for High Drug Loading, High Nuclease Resistance, and High Receptor Accessibility Yu Zhang, Qian Dong, Jiaxiang Xiao, Xingru Fang, Wenwen Huang, Qi Li, Zhuo Chen, Honglin Liu and Weihong Tan Yu Zhang , Qian Dong , Jiaxiang Xiao , Xingru Fang , Wenwen Huang , Qi Li , Zhuo Chen , Honglin Liu and Weihong Tan https://doi.org/10.31635/ccschem.024.202404442 SectionsSupplemental MaterialAboutPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Aptamers are of great interest in biomedical applications, e.g., sensing, imaging, and targeted delivering, but face crucial challenges, particularly regarding in vivo stability. Here, we developed a nanocarrier based on polyvalent aptamer-protein, named pAPNC, made of BSA core and polyvalent XQ-2d aptamer shells. pAPNC possessed outstanding properties in biostability, signal amplification, drug-loading efficiency, and cancer cell killing. When normalised to same amounts of XQ-2d, pAPNC shows improved stability in serum and DNase I nuclease for 72 h and 96 h; exhibits a 30% higher affinity towards CD71 receptor than XQ-2d, a 5-fold improved loading efficiency of Dox molecules than XQ-2d; a prolonged in vivo imaging capability than XQ-2d in mice assays. The improved loading efficiency comes from intricate protein-DNA interactions and synergistic charge effects within DNA chains, enhanced resistance to nucleases owing to effects of stereo-hindrance, electrostatic repulsion, and gathering of XQ-2d aptamers on BSA surface. When normalised to the same and ultra-low 1.6 nM of Dox, pAPNC@Dox can damage 52.5% cancer cells, improved 49% than free Dox, and 23% than XQ-2d@Dox, which is due to the enhanced nuclease resistance and receptor accessibility. This pioneering platform holds great promise for revolutionising targeted therapeutic interventions and imaging modalities in biomedical settings. Download figure Download PowerPoint Previous articleNext article FiguresReferencesRelatedDetails Issue AssignmentNot Yet AssignedSupporting Information Copyright & Permissions© 2024 Chinese Chemical Society Downloaded 0 times PDF downloadLoading ...