School of Biological Engineering, Henan University of Technology, Zhengzhou, People's Republic of China.
Key Laboratory of Functional Molecules for Biomedical Research, Zhengzhou, People's Republic of China.
Int J Nanomedicine. 2024 Sep 2;19:8949-8970. doi: 10.2147/IJN.S472276. eCollection 2024.
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.
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.
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.
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.
RNA 干扰（RNAi）是一种广泛应用的基因干扰技术，其中小干扰 RNA（siRNA）作为一种有前途的癌症治疗工具而备受关注。然而，siRNA 存在易降解和生物利用度低等固有局限性，限制了其在癌症治疗中的疗效。为了解决这些挑战，本研究专注于开发一种能够递送 siRNA 和阿霉素的纳米载体系统（HLM-N@DOX/R），用于治疗乳腺癌。
该研究全面考察了纳米载体的各种特性，包括形状、直径、傅里叶变换红外（FT-IR）光谱、X 射线光电子能谱（XPS）、包封效率和载药量。随后，进行了体外和体内细胞毒性、细胞摄取、细胞免疫荧光、溶酶体逃逸以及小鼠肿瘤模型研究，以评估纳米载体逆转肿瘤多药耐药和抗肿瘤效果的能力。
结果表明，HLM-N@DOX/R 具有较高的包封效率和载药量，并表现出 pH/氧化还原双重响应的药物释放特性。体外和体内研究表明，HLM-N@DOX/R 通过抑制 P-gp 的表达达到 80%，抑制 MDR 肿瘤生长 71%，消除 P 蛋白介导的多药耐药。
综上所述，HLM-N 作为 DOX 和 P-gp siRNA 的有效靶向共递药系统具有巨大潜力，为克服乳腺癌中的多药耐药提供了一种有前途的策略。
