Strategies to release doxorubicin from doxorubicin delivery vehicles

Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs and has been successfully applied in clinics to treat haematological malignancies and a broad range of solid tumours. However, the clinical applications of DOX have long been limited due to severe dose-dependent toxicities. Recent advances in the development of DOX delivery vehicles have addressed some of the non-specific toxicity challenges associated with DOX. These DOX-loaded vehicles are designed to release DOX in cancer cells effectively by cutting off linkers between DOX and carriers response to stimuli. This article focuses on various strategies that serve as potential tools to release DOX from DOX-loaded vehicles efficiently to achieve a higher DOX concentration in tumour tissue and a lower concentration in normal tissue. With a deeper understanding of the differences between normal and tumour tissues, it might be possible to design ever more promising prodrug systems for DOX delivery and cancer therapy in the near future.