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

Area of Science:

• Pharmaceutics
• Biomedical Engineering
• Renal Medicine

Background:

• Drug delivery systems (DDS) require targeted modifications for improved efficacy.
• Acute kidney injury (AKI) pathology involves specific cell subtypes crucial for progression.
• Identifying key cell subtypes and their markers is essential for targeted therapies.

Purpose of the Study:

• To develop a bionic DDS guided by single-cell RNA sequencing (scRNA-seq) for targeting the Key Cell Subtype for Pathological Progression (KCS-PP) in AKI.
• To design and prepare a novel DDS, BRNCs@AMMOs, specifically targeting renal tubular epithelial cells (PTIs) in AKI.
• To evaluate the in vitro and in vivo efficacy of the PTI-targeting bionic DDS for AKI treatment.

Main Methods:

• Utilized scRNA-seq to identify PTIs as the KCS-PP for AKI.
• Identified VCAM1 and ICAM1 as Targeting Drug Delivery Mediators (TDDMs) for PTIs.
• Custom-designed and prepared bionic DDS (BRNCs@AMMOs) for PTI targeting.

Main Results:

• BRNCs@AMMOs demonstrated 3.2 times greater adhesion to PTI model cells compared to normal cells in vitro.
• In vivo, BRNCs@AMMOs showed 3.7 times higher mean fluorescence intensity (MFI) in AKI kidneys versus sham kidneys 6 hours post-injection.
• The DDS exhibited prolonged retention in both PTI model cells and AKI kidneys.

Conclusions:

• The custom-designed PTI-targeting bionic DDS, BRNCs@AMMOs, is effective for AKI treatment.
• This approach demonstrates the potential for scRNA-seq guided, custom DDS development for various diseases.
• BRNCs@AMMOs offers a promising strategy for targeted drug delivery in AKI, with implications for personalized medicine.