| Summary: | The transcription factor nuclear factor erythroid 2‐related factor 2 (Nrf2) is considered as<br />the master regulator of antioxidant and cytoprotective gene expressions. Moreover, it plays a<br />pivotal role in cancer progression. Nrf2 mediates the adaptive response which contributes to the<br />resistance to chemotherapeutic pro‐oxidant drugs, such as cisplatin (CDDP), in various tumors,<br />including bladder cancers. For this reason, Nrf2 could be a promising target to overcome<br />chemoresistance. There are several known Nrf2 pharmacological inhibitors; however, most of<br />them are not specific. The use of a specific small interfering RNA (siRNA) targeting the Nrf2 gene<br />(siNrf2) loaded into nanovehicles is an attractive alternative, since it can increase specificity. This<br />study aimed to evaluate the biological activity of siNrf2 loaded on guanidine‐terminated<br />carbosilane dendrimers (GCDs) in overcoming CDDP resistance in bladder cancer cells with a<br />high level of Nrf2. Parameters such as viability, proliferation, apoptosis, migration, and oxidative<br />stress level were taken into account. Results demonstrated that siNrf2‐GCD treatment sensitized<br />CDDP‐resistant cells to CDDP treatment. Moreover, data obtained by treating the non‐cancerous<br />human kidney HK‐2 cell line strongly suggest a good safety profile of the carbosilane dendrimers<br />loaded with siNrf2. In conclusion, we suggest that siNrf2‐GCD is a promising drug delivery<br />system for gene therapy to be used in vivo; and it may represent an important tool in the therapy<br />of CDDP‐resistant cancer.
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