Multi-responsive co-assembled polyurethane nanomicelles as anticancer drug delivery carriers

In order to obtain a kind of anticancer drug delivery carriers with good stability in blood circulation, high cellular uptake, and controlled drug release ability, folate-modified polyurethane with disulfide bonds and amino groups (FPUSN) and polyurethane with carboxyl groups (PUC) were respectively synthesized. FPUSN and PUC could co-assemble in water to form nanomicelles (FPUSN/PUC) via electrostatic interaction. When the mass ratio of FPUSN to PUC was 12, FPUSN/PUC-12 micelles had obvious negative-to-positive charge-reversal property with decreasing pH from 7.4 to 5.0. Doxorubicin-loaded micelles (FPUSN/PUC-12@DOX) with negative charges showed excellent stability under simulated normal physiological condition. However, the charge-reversal happened at pH 6.5 and positive charges increased with the pH decrease. When the glutathione concentration was 10 mM, the structure of FPUSN/PUC-12@DOX micelles was broken. So FPUSN/PUC-12@DOX micelles exhibited significant acid/reduction-sensitive drug release properties and then DOX could be rapidly released in simulated tumor intracellular environment. Cellular experimental results demonstrated that FPUSN/PUC-12 micelles could enhance cellular uptake under acid condition and FPUSN/PUC-12@DOX micelles had better anti-proliferation effect against HGC-27 cells at pH 6.5 than that at pH 7.4 owing to multi-responsive synergistic effects. Therefore, FPUSN/PUC micelles will have great application potential as drug delivery carriers for enhancing anticancer efficacy.