Stimulus-responsive sequential release systems for drug and gene delivery

In recent years, a range of studies have been conducted with the aim to design and characterize delivery systems that are able to release multiple therapeutic agents in controlled and programmed temporal sequences, or with spatial resolution inside the body. This sequential release occurs in response to different stimuli, including changes in pH, redox potential, enzyme activity, temperature gradients, light irradiation, and by applying external magnetic and electrical fields. Sequential release (SR)-based delivery systems, are often based on a range of different micro- or nanocarriers and may offer a silver bullet in the battle against various diseases, such as cancer. Their distinctive characteristic is the ability to release one or more drugs (or release drugs along with genes) in a controlled sequence at different times or at different sites. This approach can lengthen gene expression periods, reduce the side effects of drugs, enhance the efficacy of drugs, and induce an anti-proliferative effect on cancer cells due to the synergistic effects of genes and drugs. The key objective of this review is to summarize recent progress in SR-based drug/gene delivery systems for cancer and other diseases.