Synthesis and Evaluation of Trehalose-Based Mertansine Warheads for Bacillus Calmette-Guérin Delivery of Anticancer Agents.

Nonmuscle invasive bladder cancer (NMIBC) accounts for 75% of bladder cancer cases, with Bacillus Calmette-Guérin (BCG) immunotherapy as the gold standard for high-risk patients. BCG elicits a robust immune response but is limited by adverse effects and resistance. To enhance its efficacy, a trehalose-based conjugation strategy is developed, tethering a cytostatic agent to BCG via a cleavable disulfide linker. This system enables selective drug integration into the BCG envelope and controlled release in tumor cells, aiming to improve therapeutic precision while minimizing toxicity. This approach combines immunotherapy with targeted chemotherapy, offering a promising strategy for NMIBC treatment.