A multifunctional M1-like cell vehicle to intravesically deliver ICG for photodynamic therapy of bladder cancer

Intravesical drug delivery systems often fail to satisfy the requirement of multifunctionality in one entity, including mucoadhesion, tumor-selective binding and deep tumor-penetration. In this work, we engineered the surface of M1-like macrophages with both tumor-targeted and mucoadhesive ligands (R11) to develop a multifunctional cell vehicle (M1^R11) for intravesical delivery of ICG. Remarkably, M1^R11 corrected the lysosomal trafficking of ICG, directed it to enter the transcellular pathway and thereby enhance its intra-tumoral penetration. When intravesically applied, the M1^R11-delivered ICG displayed much improved photodynamic efficacy, ultimately eradicating orthotopic bladder tumors in most cases and achieving complete pathological response.