Hydrogen-bond super-amphiphile based drug delivery system: design, synthesis, and biological evaluation

Drug delivery systems (DDSs) show great application prospects in tumor therapy. So far, physical encapsulation and covalent grafting were the two most common strategies for the construction of DDSs. However, physical encapsulation-based DDSs usually suffered from low drug loading capacity and poor stability, and covalent grafting-based DDSs might reduce the activity of original drug, which greatly limited their clinical application. Therefore, it is of great research value to design a new DDS with high drug loading capacity, robust stability, and original drug activity. Herein, we report a super-amphiphile based drug delivery system (HBS-DDS) through self-assembly induced by hydrogen bonds between amino-substituted N-heterocycles of the 1,3,5-triazines and hydrophilic carmofur (HCFU). The resulting HBS-DDS had a high drug loading capacity (38.1%) and robust stability. In addition, the drug delivery system exhibited pH-triggered size change and release of drugs because of the pH responsiveness of hydrogen bonds. In particular, the anticancer ability test showed that the HBS-DDS could be efficiently ingested by tumor cells, and its half-maximal inhibitory concentration (IC₅₀ = 3.53 μg mL^-1) for HeLa cells was close to that of free HCFU (IC₅₀ = 5.54 μg mL^-1). The hydrogen bond-based DDS represents a potential drug delivery system in tumor therapy.