Most solid tumors contain a tumor-specific microenvironment that is characterized by low pO2, also known as hypoxia. Owing to the rapid proliferation of cancer cells, the tumor quickly exhausts the nutrient and oxygen supplied from the vasculature, and becomes hypoxic. Targeting hypoxia is considered as the best validated yet not extensively exploited strategy in cancer therapy. Recently, a research article entitled "an effective tumor-targeting strategy utilizing hypoxia-sensitive siRNA delivery system for improved anti-tumor outcome" in Prof. Gao Zhonggao's group in the State Key Laboratory of Bioactive Substance and Function of Natural Medicines has been published by the international authorizedjournal Acta Biomaterialia(IF 6.008).
2-nitroimidazole (NI), a hydrophobic component that can be converted to hydrophilic 2-aminoimidazole (AI) through bioreduction under hypoxic conditions, was conjugated to the alkylated polyethyleneimine (bPEI1.8k-C6) to form amphiphilic bPEI1.8k-C6-NI polycations, which were able to condense negatively charged siRNA molecules to form bPEI1.8k-C6-NI/siRNA polyplexes. Owing to the special structure, the polyplexes had improved stability, resulted in increased cellular uptake. After being transported into the hypoxic tumor cells, the selective nitro-to-amino reduction would cause structural change to facilitate the siRNA dissociation in the cytoplasm, for enhanced gene silencing efficiency ultimately. Therefore, the conflict between the extracellular stability and the intracellular siRNA release ability of the siRNA delivery system was solved by introducing the hypoxia-responsive unit. Consequently, the novel siRNA delivery system shown remarkable anti-tumor effect in tumor-bearing mice, indicating that the hypoxia-sensitive siRNA delivery system had great potential for tumor-targeted therapy. With the growing understanding of tumor hypoxia, it is likely that hypoxia-responsive siRNA delivery system will provide a new choice for tumor therapy.
Currently, this article is available online. ”
“An effective tumor-targeting strategy utilizing hypoxia-sensitive siRNA delivery system for improved anti-tumor outcome” Online address.
