Polymer-DNA assembled nanoflower for targeted delivery of dolastatin-derived microtubule inhibitors

Abstract

Dolastatin derivatives possess excellent anticancer activity and have been translated into clinical trials for cancer therapy. Drug delivery systems enable dolastatin derivatives to break the limitation of instability during blood circulation and ineffective cell internalization in the application. Nevertheless, their potential has not been thoroughly established because of the limited loading efficacy and complicated chemical modification. Herein, we rationally propose a rolling circle amplification-based polymer-DNA assembled nanoflower for targeted and efficient delivery of dolastatin-derived drugs to achieve efficient anticancer therapy. The polymer-DNA assembled nanoflower with targeted aptamer conjugate is widely applicable for loading dolastatin-derived drugs with high encapsulation efficiency. The developed monomethyl auristatin E (MMAE) loaded PN@M exhibited increased cellular uptake and enhanced inhibitory effect, especially in multidrug-resistant tumor cells. The results of in vivo anticancer effects indicate that nanoflower as a dolastatin derivatives delivery system holds considerable potential for the treatment of malignant cancer.