Bladder cancer is a leading cause of cancer-related mortality, yet current intravesical drug delivery methods often suffer from poor retention times in the bladder. Gecko feet-like nanomaterials offer the potential to overcome this challenge, however conventional methods to fabricate high surface area nanomaterials for drug delivery require a complex and expensive manufacturing process. In this work, a simple fluid flow template process for manufacturing soft dendritic particles (SDPs) composed of poly(lactic-co-glycolic acid) (PLGA) with a chitosan coating for enhanced adhesion to epithelial tissues via van der Waals interactions is reported. These biodegradable SDPs encapsulate chemotherapeutic agents and are administered using an alginate hydrogel, allowing for precise deposition and sustained drug release. The results demonstrate that SDPs adhere to mouse and human cancer cells and mouse soft tissues for several days. The SDPs effectively encapsulate and release clinically-utilized chemotherapeutic drugs such as gemcitabine, docetaxel, and methotrexate, exhibiting superior cancer cell killing in vitro. In murine models, gemcitabine-loaded SDPs instilled into tumor-bearing bladders elicited a stronger CD45+ immune cell response than control groups while maintaining minimal toxicity. This work presents a scalable, biomimetic drug delivery platform with prolonged retention and controlled drug release, offering a versatile strategy for improving bladder cancer treatment.
