Superamphiphile Based Cross-Linked Small-Molecule Micelles for pH-Triggered Release of Anticancer Drugs

A new superamphiphile based cross-linked small-molecule micelle (SA-CSM) is developed for pH-triggered release of anticancer drugs. This strategy revolves around the use of a noncovalent superamphiphile formed by the elaborate zwitterion 1 and anticancer drug doxorubicin (DOX) via their “spontaneous attraction” of carboxylic acid and amino group. The superamphiphiles self-assemble into micelles in water, which were further stabilized by cross-linking the surface via the thiol-acrylate Michael addition to achieve the establishment of the pH-sensitive SA-CSMs. The biological evaluation shows that the new drug delivery system exhibits highly efficient anticancer efficacy both in vitro, on the HeLa cancer cell line, and in vivo, on the HeLa xenograft model, while suppressing the inherent toxicity of the employed chemotherapeutics. Compared with the reported covalent amphiphile based CSMs, the noncovalent superamphiphile based CSMs not only have comparable drug loading content (up to 45.0%), robust stability, and superior predictable biosafety but also feature nonchemical synthesis, low production cost, specific stimulus response, and anticancer activity of the original drugs and thus represent a good example for clinical application.