Engineered exosomes deliver structurally optimized toad BAX to reactivate mitochondrial apoptosis in colorectal cancer

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Mitochondrial apoptosis evasion in colorectal cancer (CRC) is primarily driven by overexpression of anti-apoptotic BCL-2 family proteins.
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Toad BAX from Xenopus laevis effectively binds human BCL-2, triggering mitochondrial outer membrane permeabilization and apoptosis in CRC cells.
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A rationally designed triple mutant of toad BAX showed enhanced affinity for BCL-2 and superior anti-tumor activity compared to wild-type toad BAX.
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Exosome-mediated delivery of optimized BAX effectively targeted CRC cells, inhibited tumor growth, and extended survival in preclinical models.
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This study provides a preclinical foundation for using engineered exosomes to deliver pro-apoptotic proteins as a strategy against apoptosis-evasive solid tumors.

Frontiers In Oncology

by Xinqiang Xu, Hongjie Wu, Yixin Yan, Hongwei Cui, Tianyi Yu, Ye Yang, Zhendong Deng, Jinjun Qian
June 24, 2026

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