Park Jiwon, Kim Seoyoung, Kim Tae-Il
Department of Agriculture, Forestry and Bioresources, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Department of Biosystems & Biomaterials Science and Engineering, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Pharmaceutics. 2023 Feb 20;15(2):708. doi: 10.3390/pharmaceutics15020708.
Hydroxyethyl cellulose (HEC), widely known for its biocompatibility and water solubility, is a polysaccharide with potential for pharmaceutical applications. Here, we synthesized polyethylenimine2k (PEI2k)-conjugated hydroxyethyl cellulose (HECP2k) for doxorubicin/Bcl-2 siRNA co-delivery systems. HECP2ks were synthesized by reductive amination of PEI2k with periodate-oxidized HEC. The synthesis of the polymers was characterized using H NMR, C NMR, primary amine quantification, FT-IR, and GPC. Via agarose gel electrophoresis and Zeta-sizer measurement, it was found that HECP2ks condensed pDNA to positively charged and nano-sized complexes (100-300 nm, ~30 mV). The cytotoxicity of HECP2ks was low and HECP2k 10X exhibited higher transfection efficiency than PEI25k even in serum condition, showing its high serum stability from ethylene oxide side chains. Flow cytometry analysis and confocal laser microscopy observation verified the superior cellular uptake and efficient endosome escape of HECP2k 10X. HECP2k 10X also could load Dox and Bcl-2 siRNA, forming nano-particles (HECP2k 10X@Dox/siRNA). By median effect analysis and annexin V staining analysis, it was found that HECP2k 10X@Dox/siRNA complexes could cause synergistically enhanced anti-cancer effects to cancer cells via induction of apoptosis. Consequently, it was concluded that HECP2k possesses great potential as a promising Dox/Bcl-2 siRNA co-delivery carrier.
羟乙基纤维素（HEC）以其生物相容性和水溶性而广为人知，是一种具有药物应用潜力的多糖。在此，我们合成了用于阿霉素/Bcl-2 siRNA共递送系统的聚乙烯亚胺2k（PEI2k）共轭羟乙基纤维素（HECP2k）。HECP2k是通过PEI2k与高碘酸盐氧化的HEC进行还原胺化反应合成的。使用1H NMR、13C NMR、伯胺定量、FT-IR和GPC对聚合物的合成进行了表征。通过琼脂糖凝胶电泳和Zeta电位仪测量发现，HECP2k将pDNA浓缩成带正电荷的纳米级复合物（100 - 300 nm，约30 mV）。HECP2k的细胞毒性较低，即使在血清条件下，HECP2k 10X的转染效率也高于PEI25k，表明其来自环氧乙烷侧链的高血清稳定性。流式细胞术分析和共聚焦激光显微镜观察证实了HECP2k 10X具有优异的细胞摄取能力和有效的内体逃逸能力。HECP2k 10X还可以负载阿霉素和Bcl-2 siRNA，形成纳米颗粒（HECP2k 10X@Dox/siRNA）。通过中位效应分析和膜联蛋白V染色分析发现，HECP2k 10X@Dox/siRNA复合物可通过诱导细胞凋亡对癌细胞产生协同增强的抗癌作用。因此，得出结论，HECP2k作为一种有前景的阿霉素/Bcl-2 siRNA共递送载体具有巨大潜力。
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