Hybrid-Driven Bacillus Calmette-Guérin Carrier for Targeted Immuno-Chemo Combo Therapy in Bladder Cancer.

Combination therapy is a promising approach to enhancing antitumor efficacy and overcoming multidrug resistance. Intravesical instillation of Bacillus Calmette-Guérin (BCG) combined with chemotherapy has been employed to improve bladder cancer treatment efficacy, but outcomes are often limited by high-dose drug irritation, poor patient tolerance, and insufficient targeting. To overcome these limitations, we propose a microrobot (MR)-based targeted drug delivery strategy for precise co-delivery of BCG and paclitaxel to bladder tumors, facilitating sustained drug release and minimizing off-target effects. The MRs are fabricated using a layer-by-layer assembly technique, incorporating antitumor drugs, magnetic nanoparticles, and viable BCG. Under the synergistic action of external magnetic fields and hydrogen microbubbles generated through chemical reactions, the MRs achieve targeted navigation and effective accumulation within the 3-dimensional tumor microenvironment. Subsequently, the combined chemotherapeutic and immunostimulatory effects effectively inhibit tumor progression. This approach not only minimizes off-target effects but also facilitates sustained drug release. Additionally, a wearable magnetic fixation device based on a Halbach array is employed to fixate the MRs at the targeted region, further improving drug retention and enhancing therapeutic efficacy. The experimental results demonstrate that this MR-based delivery system holds considerable potential for clinical translation into combination therapies for bladder cancer.