Hybrid Liposome-MSN System with Co-Delivering Potential Effective Against Multidrug-Resistant Tumor Targets in Mice Model

Yanan Yang,1,* Shuoye Yang,1,2,* Beibei Zhang,1 Jinpeng Wang,1 Di Meng,1 Lan Cui,1,2 Lu Zhang1,2 1School of Biological Engineering, Henan University of Technology, Zhengzhou, People’s Republic of China; 2Key Laboratory of Functional Molecules for Biomedical Research, Zhengzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuoye Yang, School of Biological Engineering, Henan University of Technology, Lianhua Street, Gaoxin District, Zhengzhou, 450001, People’s Republic of China, Tel/Fax: +86-371-67756513, Email [email protected]: RNA interference (RNAi) stands as a widely employed gene interference technology, with small interfering RNA (siRNA) emerging as a promising tool for cancer treatment. However, the inherent limitations of siRNA, such as easy degradation and low bioavailability, hamper its efficacy in cancer therapy. To address these challenges, this study focused on the development of a nanocarrier system (HLM-N@DOX/R) capable of delivering both siRNA and doxorubicin for the treatment of breast cancer.Methods: The study involved a comprehensive investigation into various characteristics of the nanocarrier, including shape, diameter, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), encapsulation efficiency, and drug loading. Subsequently, in vitro and in vivo studies were conducted on cytotoxicity, cellular uptake, cellular immunofluorescence, lysosome escape, and mouse tumor models to evaluate the efficacy of the nanocarrier in reversing tumor multidrug resistance and anti-tumor effects.Results: The results showed that HLM-N@DOX/R had a high encapsulation efficiency and drug loading capacity, and exhibited pH/redox dual responsive drug release characteristics. In vitro and in vivo studies showed that HLM-N@DOX/R inhibited the expression of P-gp by 80%, inhibited MDR tumor growth by 71% and eliminated P protein mediated multidrug resistance.Conclusion: In summary, HLM-N holds tremendous potential as an effective and targeted co-delivery system for DOX and P-gp siRNA, offering a promising strategy for overcoming MDR in breast cancer.Keywords: mesoporous silica nanoparticles, multidrug resistance, small interfering RNA, doxorubicin, hybrid nanoparticles