Shi Jinjun/Omid C/Teng Lesheng Nano Lett: Dual hypoxia targeting RNAi nano-drugs for precise tumor treatment
As a sign of solid tumors, hypoxia has guiding significance in inhibiting tumor growth, metastasis and drug resistance by regulating the expression of hypoxia-related genes. Hypoxia also represents a tumor-specific stimulus, which has been used to develop prodrugs and corresponding drug delivery systems. Cell division cycle gene 20 (CDC20) plays an oncogene role in tumorigenesis. It has been confirmed that CDC20 mRNA is significantly up-regulated in tumors and adjacent tissues of breast cancer patients, and is positively correlated with tumor hypoxia. Here, Shi Jinjun, Omid C. Farokhzad, and Teng Lesheng, School of Life Sciences, Jilin University, Harvard Medical School, collaborated to prepare a hypoxia-responsive nanoparticle through the self-assembly of 2-nitroimidazole-modified peptides and cationic lipid compounds. (HRNP), used to carry siRNA targeting the tumor-promoting gene CDC20, which is related to hypoxia in the treatment of breast cancer. HRNP-mediated targeted delivery of siCDC20 fully silences the expression of CDC20, showing a strong anti-tumor effect.
This article uses hypoxia-responsive siRNA nanoparticles to silence hypoxia-related tumor-promoting genes. Through bioinformatics analysis, the authors found that CDC20 is up-regulated in tumor tissues of breast cancer patients and is related to tumor hypoxia. In vitro studies have shown that under hypoxic conditions, CDC20 has a higher level of expression in breast cancer cells. The authors developed a 2-nitroimidazole-modified polypeptide nanoparticle for the delivery of siRNA specifically targeting hypoxia response to CDC20. HRNP/siCDC20 surface pegylation, small size, prolonged blood circulation, high tumor accumulation, CDC20 has a good silencing effect, and has a significant inhibitory effect on tumor growth. This dual hypoxia targeting strategy provides a brand new idea for precise cancer treatment.
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