A responsive core/shell fiber co-delivering Bcl-2 siRNA and doxorubicin hydrochlo ride for combined tumor therapy

The core/shell structure fibrous membrane loaded with Bcl-2 siRNA and doxorubicin hydrochloride was prepared by coaxial electrospinning technology, which is a pH-responsive local drug delivery system for the synergistic treatment of breast cancer. Doxorubicin hydrochloride and Bcl-2 siRNA were loaded into pH-responsive metal-framework material zeolite imidazole framework-8 and mesoporous polydopamine modified by polyethyleneimine1.8k to obtain doxorubicin hydrochloride -encapsulated zeolite imidazole framework-8 nanoparticles and Bcl-2 siRNA-adsorbed mesoporous polydopamine nanoparticles, respectively. Fibrous membrane single-loaded with doxorubicin hydrochloride could release more drug under acidic condition than neutral condition, resulting in less damage to surrounding normal cells. The cytotoxicity of free doxorubicin hydrochloride, naked RNA, and three drug-loaded fibrous membranes was investigated using human breast cancer MCF-7 cells. The results showed that Bcl-2 siRNA adsorbed by mesoporous polydopamine modified by polyethyleneimine1.8k and then loaded onto fibers enhanced its killing effect on MCF-7 cells. Western blot analysis confirmed that Bcl-2 protein expression was significantly reduced in MCF-7 cells when treated with the core/shell fiber membrane co-loaded with Bcl-2 siRNA and doxorubicin hydrochloride, verifying the effective release of siRNA and its gene silencing activity. Compared with the survival rates of MCF-7 cells treated with doxorubicin hydrochloride-loaded fibrous membrane (49.42%) and Bcl-2 siRNA loaded fibrous membrane (60.31%), the survival rate of MCF-7 cells treated with the core/shell fiber membrane co-loaded with Bcl-2 siRNA and Doxorubicin hydrochloride was 27.99%, indicating that the dual drug-loaded core/shell fiber membrane could achieve a significant synergistic inhibitory effect on breast cancer cells.