Using self-associating supramolecular amphiphiles as a novel enhancer of anticancer drug delivery to treat non-muscle invasive bladder cancer

Non-muscle invasive bladder cancer (NMIBC) represents up to 70% of the 10,500 new bladder cancer diagnoses made each year in the UK. High recurrence rates are the most significant unmet clinical need of NMIBC, with up to 75% of patients predicted to have their cancer recur within five years post-remission. This project addresses this unmet need by assessing a novel series of supramolecular self-associating amphiphiles (SSA) for their ability to enhance the delivery and efficacy of the anticancer drugs mitomycin C and olaparib. Using the UM-UC-3 cell line as an in vitro model for NMIBC, SSAs and anticancer drugs were delivered in two primary methodologies: as a co-formulated treatment, and sequential treatment. Consistent synergy was observed when cells were sequentially treated with 48 followed by olaparib, as well as with 56 or 57 followed by mitomycin C. However, coformulating 48 and olaparib showed no statistically significant difference compared to the single agent control with ANOVA and post-hoc Dunnett’s test. The synergy observed across different SSA-drug combinations suggests that this technology can quantitatively enhance the efficacy of existing treatments for NMIBC, potentially improving patient outcomes by reducing cancer recurrence.