Customized Design and Preparation of Bionic Drug Delivery System Leveraging Single-Cell RNA Sequencing for Precisely...

Drug delivery system (DDS) is an important branch of pharmaceutics. Rational modification of the physicochemical properties of DDSs can further improve their targeting efficiency. Herein, a bionic DDS is reported for AKI that is scRNA-seq-guided, custom-designed, and prepared, targeting the Key Cell Subtype for Pathological Progression (KCS-PP) of acute kidney injury (AKI). Specifically, scRNA-seq is utilized to identify a specific renal tubular epithelial cell subtype (PTIs) as the KCS-PP for AKI from numerous cellular subtypes. Additionally, specific cell adhesion molecules (VCAM1 and ICAM1) are identified as the Targeting Drug Delivery Mediators (TDDMs) for PTIs from a list of 1000 marker genes of PTIs. Based on this progress, PTI-targeting bionic DDS, named BRNCs@AMMOs is custom-designed and prepared, and used them for AKI treatment in vitro and in vivo. In vitro, BRNCs@AMMOs shows that its adhesion ability in PTI model cells is 3.2 times that in normal cells. In vivo, 6 h after renal pelvis injection, the MFI of BRNCs@AMMOs-DiI in AKI kidneys is 3.7 times that of sham kidneys. The findings demonstrate that BRNCs@AMMOs exhibits prolonged retention in PTI model cells and AKI kidneys. Overall, the custom-designed and prepared PTI-targeting bionic DDS, may promote the customized design and preparation of DDSs for different diseases and targets, is reported.