■RNA干扰(RNAi)是一种广泛使用的基因干扰技术,小干扰RNA(siRNA)正在成为一种有前途的癌症治疗工具。然而,siRNA的固有局限性,如易降解和低生物利用度,阻碍其在癌症治疗中的疗效。为了应对这些挑战,这项研究的重点是开发一种纳米载体系统(HLM-N@DOX/R),该系统能够同时提供siRNA和阿霉素以治疗乳腺癌。
■这项研究涉及对纳米载体的各种特性进行全面调查,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),封装效率,和药物装载。随后,体外和体内研究进行了细胞毒性,细胞摄取,细胞免疫荧光,溶酶体逃脱,和小鼠肿瘤模型来评估纳米载体在逆转肿瘤多药耐药和抗肿瘤作用中的功效。
■结果表明,HLM-N@DOX/R具有较高的包封率和载药能力,并表现出pH/氧化还原双重响应药物释放特性。体内外研究表明,HLM-N@DOX/R对P-gp表达的抑制作用达80%,抑制71%的MDR肿瘤生长并消除P蛋白介导的多药耐药。
■总之,HLM-N作为DOX和P-gpsiRNA的有效和靶向共递送系统具有巨大潜力,为克服乳腺癌的MDR提供了一个有希望的策略。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.