Amphiphilic Dendrimer-Based Self-Assembled Nanodrug for Responsive Drug Delivery and Chemotherapy

Chemotherapy continues to be a mainstay of cancer therapy. However, the anticancer efficacy of chemotherapy drugs is greatly restricted by their side effects and resistance. Nanotechnology-based combination therapy is expected to improve chemotherapy by enhancing anticancer drug efficacy, reducing drug toxicity, and overcoming drug resistance. In this study, we developed an original nanoprodrug based on an ibuprofen-modified amphiphilic dendrimer (AIP), which could self-assemble into nanoparticles to codeliver the anticancer agent doxorubicin. Owing to the protonation of amine units in amphiphilic dendrimers, the resulting nanosystem (AIP@DOX) could control the pH-stimulated release of loaded cargos in the acidic tumor microenvironment. Importantly, AIP@DOX not only significantly facilitated the cellular uptake and retention of doxorubicin but also notably decreased the drug efflux to combat drug resistance, both of which contribute to enhanced drug potency. Moreover, the high selectivity of AIP@DOX obviously reduced doxorubicin-based toxicity and markedly prolonged the survival of the mice. Benefiting from the advantageous features of both combination therapy and nanotechnology-based drug delivery, this chemo/anti-inflammatory combination nanosystem constitutes a potent therapeutic candidate for cancer treatment. This study also highlights the promise of self-assembling amphiphilic dendrimer-based vesicles for drug delivery in combination therapy to enhance drug potency.