Tyrosinase-loaded Multicompartment Microreactor toward Melanoma Depletion

Melanoma is a malignant skin cancer occurring with increasing prevalence with no effective treatment. A unique feature of melanoma cells is that they require higher concentrations of L-tyrosine (L-tyr) for expansion than normal cells. As such, it has been demonstrated that dietary L-tyr restriction lowers systemic L-tyr and suppresses melanoma advancement in mice. Unfortunately, this diet is not well tolerated by humans. An alternative approach to impede melanoma progression will be to administer the enzyme tyrosinase (TYR) which converts L-tyr into melanin. Herein, a multicompartment carrier consisting of a polymer shell entrapping thousands of liposomes is employed to act as a microreactor depleting L-tyr in the presence of melanoma cells. It is shown that the TYR enzyme can be incorporated within the liposomal subunits with preserved catalytic activity. Aiming to mimic the dynamic environment at the tumor site, L-tyr conversion is conducted by co-culturing melanoma cells and microreactors in a microfluidic set-up with applied intra-tumor shear stress. It is demonstrated that the microreactors are concurrently depleting L-tyr, which translates into inhibited melanoma cell growth. Thus, the first microreactor where the depletion of a substrate translates into anti-tumor properties in vitro is reported.