Rapid screening of multi-target antitumor drugs by nonimmobilized tumor cells/tissues capillary electrophoresis

Area of Science:

• Biochemistry and Biophysics
• Analytical Chemistry
• Pharmacology

Background:

• Traditional drug screening methods often use purified targets, potentially missing interactions with native protein structures.
• Tumor microenvironments (TME) present complex cellular and tissue targets that are challenging to simulate in vitro.
• Existing methods may not adequately capture the multi-target interactions crucial for effective antitumor drug development.

Purpose of the Study:

• To develop a new capillary electrophoresis (CE) method for screening multi-target antitumor drugs using non-immobilized tumor cells and tissues.
• To maintain the natural structure and active conformation of target proteins under near-physiological conditions.
• To identify effective drug combinations with enhanced targeting, efficacy, and reduced toxicity.

Main Methods:

• Established a non-immobilized tumor cells/tissues capillary electrophoresis system simulating the tumor physiological environment.
• Studied interactions between Aidi injection (ADI) components and tumor cells/tissues, optimizing experimental conditions.
• Performed in vitro and in vivo antitumor activity assays and molecular docking studies.

Main Results:

• Identified seven ADI components binding to A549 cells, with five showing specific interaction with tumor tissues.
• Calculated binding kinetic parameters (K, ka, kd, k') for identified interactions.
• Discovered a new drug combination demonstrating higher targeting, improved efficacy, and lower toxic side effects.

Conclusions:

• The developed CE method is valid and feasible for screening multi-target antitumor drugs using intact biological samples.
• The method preserves the native state of target proteins, enabling more biologically relevant drug interaction studies.
• The approach is adaptable for high-throughput drug screening using capillary array electrophoresis.