A novel pH-responsive system based on aldehyde-bearing dextran derivatives (ODEX or FDEX) was designed to use as gene carrier shielding. Through pH sensitive Schiff base bonds between amino groups of PEI (in PEI/DNA polyplex) and aldehyde groups of dextran derivatives, PEI/DNA polyplex could be shielded and further condensed to obtain an effectively decreasing ζ-potential with smaller size. Schiff base bonds were pH-responsive, which were relatively stable in neutral environment but were deformed in slightly acidic and acidic environments. Through use of this characteristic, the PEI/DNA polyplex was effectively shielded during circulation in the body, and upon arrival at the tumor, the slightly acid pH triggered the breaking of Schiff base bonds to expose the positive PEI/DNA polyplex, which further interacted with tumor cell membranes, achieving efficient gene expression. Use of such characteristics could effectively address the high transfection efficiency versus stability dilemma of gene carriers. FDEX/PEI/DNA nanoparticles not only mediate higher cellular uptake and transfection efficiency in vitro but also effectively accumulate in tumors with gene expression in vivo higher than that of the ODEX analogues. As a result, this pH-responsive system is a promising strategy for cancer therapy.

中文翻译：

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基于动态共价化学的pH响应型天然高分子基因传递屏蔽系统

基于含醛的葡聚糖衍生物（ODEX或FDEX）的新型pH响应系统被设计用作基因载体屏蔽。通过PEI（在PEI / DNA多聚体中）的氨基和右旋糖酐衍生物的醛基之间的pH敏感席夫碱键，可以将PEI / DNA多聚体屏蔽并进一步缩合以获得较小尺寸的有效降低的ζ电位。席夫碱键具有pH响应性，在中性环境中相对稳定，但在弱酸性和酸性环境中会变形。通过利用这一特性，PEI / DNA复合体在体内循环过程中得到了有效的屏蔽，到达肿瘤后，微酸性pH触发席夫碱键的断裂，从而暴露出阳性的PEI / DNA复合体，从而进一步相互作用带有肿瘤细胞膜 实现有效的基因表达。利用这些特性可以有效解决基因载体的转染效率与稳定性难题。FDEX / PEI / DNA纳米粒子不仅可以在体外介导更高的细胞摄取和转染效率，而且还可以有效地在体内蓄积其体内基因表达高于ODEX类似物的基因表达。结果，这种pH响应系统是用于癌症治疗的有前途的策略。