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Abstract Bladder perfusion chemotherapy remains the standard treatment for bladder cancer, yet its effectiveness is frequently limited by rapid drug clearance through urinary excretion and inadequate infiltration of immune cells into bladder tissue. To address these challenges, we developed an active-targeting nano-drug delivery system specifically designed for bladder tumors. This system utilizes a sialic acid-targeted poly (lactic-co-glycolic acid) (PLGA) platform to co-deliver doxorubicin (DOX) and the purified protein derivative (PPD) of bacillus Calmette-Guérin (BCG-PPD). By leveraging the selective binding of phenylboronic acid to sialic acid, the system enhances tumor-specific drug uptake, significantly amplifying DOX’s therapeutic efficacy and inducing immunogenic cell death. Furthermore, BCG-PPD exerts potent immunostimulatory effects, promoting dendritic cell (DC)-mediated tumor antigen processing and presentation, which in turn drives robust cytotoxic T lymphocyte (CTL) infiltration into the tumor microenvironment. The superior anti-tumor performance of this system was validated in an orthotopic bladder cancer mouse model. In conclusion, by synergistically combining targeted drug delivery with chemo-immunotherapy, our nanoparticle system presents a highly effective and promising new paradigm for bladder cancer therapy.
Zhang et al. (Sat,) studied this question.