Supramolecular engineering of polymeric nanodrugs for antitumor chemotherapy

Intravenously administered nanodrugs undergo a number of processes to generate therapeutic effects. The rational design of nanodrugs with high efficiency at every step of the drug deliver process is critical to their therapeutic efficiency. However, many reported nanodrugs that meet these requirements are too complex to prepare for practical use. Herein, we report a simplified and reproducible one step nanodrug fabrication strategy, with only two components, using supramolecular engineering. Di-adamantane-modified camptothecin was precisely synthesized as a prodrug with high purity. An amphiphilic biodegradable block copolymer with pendant β-cyclodextrin moieties on the hydrophobic block was then synthesized by controlled ring-opening polymerization and “click” chemistry. The co-self-assembly of the camptothecin prodrug and block copolymer in an aqueous medium, driven by host–guest interactions between the adamantine and β-cyclodextrin moieties, gave a camptothecin nanodrug with quantitative drug loading content and defined chemical composition. This nanodrug, which consists of a suitable size and stable core-crosslinked structure, has prolonged blood circulation and accumulates efficiently at tumor sites thus showing potent anti-tumor activity. This work provides a strategy to precisely fabricate nanodrugs that is reproducible, and which has great potential for bench-to-bedside translation.