Polydopamine, a potential mucopenetrative nanomaterial capable of multimodal therapy for bladder cancer

The high rate of treatment failure for superficial Bladder cancer is partly due to the short residence time of drugs and low uptake, both of which can be explained by urine voiding as well as the presence of a thin mucus layer... [ view full abstract ]

The high rate of treatment failure for superficial Bladder cancer is partly due to the short residence time of drugs and low uptake, both of which can be explained by urine voiding as well as the presence of a thin mucus layer on the surface of the urothelium. Hence, the development of novel therapeutics that would improve drug retention for patients with bladder cancer is significant.
The present study aims to exploit the many properties of polydopamine (PDA) to design a biodegradable muco penetrative polymeric nanocarrier of Ce6, a photosensitizer drug. PDA is hydrophilic and slightly negatively charged which minimizes hydrophobic interactions and electrostatic interactions with the negatively charged mucus mesh. Furthermore, it is a natural mimic of melanin, biocompatible, easily synthesized and capable of photothermal properties thus enabling multimodal therapy (photodynamic (PDT) and photothermal (PTT)) to increase the drug retention and hence cell kill efficacy of non-muscle invasive bladder cancer cells.
To date, we have successfully characterized and optimized PDA loaded with Ce6 in vitro and studied many parameters such as their loading capacity, stability in different media and release profiles. It has been demonstrated that PDA could effectively load up to 3 microM of Ce6 with an initial burst release and a saturation at day 7. The therapeutic effect of PDA-Ce6 has also been compared to free Ce6 and PDA alone in bladder cancer cells with a significantly higher cell kill when subjected to the dual PDT-PTT. Furthermore, preliminary studies have been performed probing the interaction between mucin and PDA. Results with the Transwell system seemed to indicate that PDA were capable of permeating through the mucus mesh.
The development of these mucopenetrative particles could possibly also be applied in other kinds of cancer or drug delivery therapy which requires passage through the mucus barrier.