Tumor-Mimic Artificial Cell Integrated With In Situ Synthetic Biology for Testing of Antitumor Drug Sensitivity.

The novel models represented by organoids are becoming the key approach to solve the ethical and efficiency problems in drug development, but the effective and low-cost models are still urgently needed. The breakthrough development of artificial cell (AC) technology and synthetic biology has made it possible. In this study, a novel AC for evaluating the efficacy of various antitumor drugs is fabricated by combining cell membrane bionic technology and in situ synthetic biology. After entering ACs, antitumor drugs targeting nucleic acid affect the gene transcription of an artificially designed ribozyme that can catalyze the cleavage of molecular beacons and generate fluorescence signals in situ, indicating the efficacy of antitumor drugs at the cellular level. Specifically, ACs constructed with cell membranes containing drug-resistant proteins show significant drug inhibition, and the 3D coded ACs established based on this method are capable of classifying cell-specific characteristics more accurately to provide support for targeted drug therapy. This platform for in situ pharmacodynamic analysis not only demonstrates the individualized penetration ability of tumor heterogeneous packaging membranes in response to tumor drugs but also fills the gap between non-living and living experiments as a supplementary strategy.