The reactive oxygen species (ROS)-responsive intelligent drug delivery system has developed rapidly in recent years. However, because of the low concentration of ROS in most types of tumor cells, it is not possible to rapidly and effectively stimulate the drug delivery system to release the active drug. Here, we introduced “sequential induced activation processes” for efficient tumor therapy by designing a new ROS-responsive drug release platform. β-Lapachone, a positively charged nitrogen mustard (NM) prodrug, and two diblock molecules (mPEG-AcMH and PAsp-AcMH) are self-assembled to form prodrug primary micelles, which are further aggregated into nanoparticles that facilitate drug codelivery. When administered by intravenous injection, the nanoparticles reach the tumor site and enter the tumor cells by endocytosis. The β-lapachone released in the tumor cells induces a large amount of H2O2, and the ROS-responsive NM prodrug is activated to form activated NM, quinone methide, and boric acid under the induction of H2O2. The activated NM leads to tumor cell apoptosis.

A new type of reduction- and pH-mediated glyco-polymeric micelles was synthesized for the antitumor drug doxorubicin (DOX) delivery in this study.

Entirely oligosaccharide-based supramolecular amphiphiles were constructed via host-guest interactions between ferrocene-terminated acetylated-maltoheptaose (Fc-AcMH) and β-cyclodextrin-terminated four-arm star maltoheptaose (MH-β-CD). The amphiphiles could self-assemble to form spherical supramolecular nanoparticles to provide efficient drug delivery platforms. The combination of a pH-sensitive covalent acetal group and the oxidation-sensitive noncovalent host-guest interaction of β-CD and ferrocene provided the obtained fully oligosaccharide-based supramolecular amphiphiles. The structures of these amphiphiles could respond to the intracellular microenvironment.