Harnessing Natural Pollen as Sustained‐Release, Mucoadhesive, and Biosafe Drug Microcapsules for Intravesical Instillation in Bladder Cancer Treatment

Abstract Intravesical instillation is essential for bladder cancer treatment, but current therapy suffers from brief drug retention and insufficient contact bladder contact. Nano‐ and micro‐sized capsules‐based drug delivery systems are expected to solve these problems, which, however, face challenges such as weak mucoadhesion, low biosafety, and processing complexity, limiting their scalable application. In this study, the power of plant pollen‐derived microcapsules, sporopollenin exine capsules (SECs) is harnessed that are produced by sequentially defatting and acidolysis sunflower pollen, to passive load with pirarubicin and achieve biosafe and high‐efficiency intravesical chemotherapy. SECs exhibit no significant toxic effects in vitro or in vivo. Taking advantage of its intrinsic microscale core–shell structure and spiny surface topography, convenient encapsulation is achieved with an efficiency of 45.3±1.43% and sustained release of the simulate drug, and strong adhesion to the bladder mucosa even after multiple urination, which reduces the instillation‐maintenance time to just 20 min. Drugs encapsulated in SECs maintained higher concentrations in the bladder for up to 5 h compared to those without SECs. In a murine orthotopic bladder cancer model, SECs enhance the intravesical chemotherapy effect of pirorubicin (increased by 38%). The study introduces an innovative, naturally occurring drug carrier for advancing future intravesical instillation therapies.