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. The schematic illustration of FPUSN/PUC micelles as anti‐cancer drug delivery carriers