A pH‐Responsive Biomimetic Nanoparticle Coated With Macrophage Membranes for Photothermal and Immunotherapy of Bladder Cancer

ABSTRACT

Tumor metastasis and recurrence are major reasons for the difficulty in curing cancer. Although some immunotherapy methods have been developed, they are still limited by immunosuppression, resulting in limited therapeutic efficacy against tumors. Here, we report a biomimetic drug delivery platform utilizing macrophage membrane‐coated pH‐responsive nanoparticles. The macrophage membrane not only targets tumor cells and tissues, but also increases in vivo retention time. The pH‐responsive nanoparticles release the drug at the tumor site, achieving a release rate of 82.5% in the acidic tumor microenvironment (pH 4.5) versus only 21.3% under physiological conditions (pH 7.2), thus enhancing drug utilization. Additionally, the internal semiconductor particle PCPDTBT can induce immunogenic cell death under external laser irradiation. Combined with the immune checkpoint inhibitor anti‐PD‐L1, this approach activates systemic immune responses, improving therapeutic outcomes for bladder cancer and inhibiting tumor recurrence. In vitro and in vivo experiments demonstrate that these biomimetic nanoparticles possess strong anti‐tumor effects, leading to complete tumor eradication and a 100% survival rate in the combination therapy group, showing great potential for clinical application.