RESUMO
Multidrug resistance (MDR) is a major obstacle limiting the effectiveness of chemotherapy against cancer. The combination strategy of chemotherapeutic agents and siRNA targeting drug efflux has emerged as an effective cancer treatment to overcome MDR. Herein, stimuli-responsive programmable tetrahedral DNA-RNA nanocages (TDRN) have been rationally designed and developed for dynamic co-delivery of the chemotherapeutic drug doxorubicin and P-glycoprotein (P-gp) siRNA. Specifically, the sense and antisense strand sequences of the P-gp siRNA, which are programmable bricks with terminal disulfide bond conjugation, are precisely embedded in one edge of the DNA tetrahedron. TDRN provides a stimuli-responsive release element for dynamic control of functional cargo P-gp siRNA that is significantly more stable than the "tail-like" TDN nanostructures. The stable and highly rigid 3D nanostructure of the siRNA-organized TDRN nanocages demonstrated a notable improvement in the stability of RNase A and mouse serum, as well as long-term storage stability for up to 4 weeks, as evidenced by this study. These biocompatible and multifunctional TDRN nanocarriers with gold nanocluster-assisted delivery (TDRN@Dox@AuNCp) are successfully used to achieve synergistic RNAi/Chemo-therapy in vitro and in vivo. This programmable TDRN drug delivery system, which integrates RNAi therapy and chemotherapy, offers a promising approach for treating multidrug-resistant tumors.
RESUMO
AIM: To investigate the transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) expressions in benign prostatic hyperplasia (BPH) and the effect of beta-radiation. METHODS: TGF-beta1 and bFGF expression was studied by means of an immunohistochemical method in nine normal prostatic (NP) tissues, 15 hyperplastic prostatic tissues and 35 hyperplastic prostatic tissues treated with 90Sr/90Y. RESULTS: The TGF-beta1 expression in the epithelium and stroma of normal prostatic tissues was 68.2 % +/- 10.5 % and 29.7 % +/- 4.6 %, respectively, while it was 64.8 % +/- 9.3 % and 28.6 % +/- 4.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, TGF-beta1 expression in the epithelia and stroma of BPH treated with 90Sr/90Y increased significantly (P <0.01). The bFGF expression in epithelia and stroma of normal prostatic tissues was 17.4 % +/- 3.7 % and 42.5 % +/- 6.8 %, respectively, and was 46.3 % +/- 8.2 % and 73.2 % +/- 12.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, expressions of bFGF in the epithelia and stroma of BPH treated with a 90Sr/90Y prostatic hyperplasia applicator decreased significantly (P <0.01). CONCLUSION: Exposure of beta-rays had noticeable effects on BPH tissues, enhancing TGF-beta1 expression and inhibiting bFGF expression.
