Effect of aggregation structures of dimeric prodrug-based carrier-free nanomedicines for tumor chemotherapy

Abstract

Dimeric prodrug-based carrier-free nanomedicines have been recognized as promising candidate for tumor chemotherapy. The molecular structure of the dimeric prodrugs has been widely investigated, including the intracellular stimuli responsibilities and their sensitivity, but their aggregation structure has not been explored by now. Here, the effect of aggregation structures of dimeric prodrug-based carrier-free nanomedicines for tumor chemotherapy was investigated with a reduction-triggered doxorubicin dimer (D-DOXss) as model. Different aggregation structures could be achieved with various fabrication strategies, by controlling the formation of the π–π stacking interactions between the conjugated anthraquinone ring in doxorubicin (DOX), leading to distinct drug release performance and in vitro anti-tumor efficacy. The finding is expected to open new ideas for the future design and development of chemotherapeutic formulations.