The inherent instability of nucleic acids within serum and the tumor microenvironment necessitates a suitable vehicle for non-viral gene delivery to malignant lesions. A specificity-conferring mechanism is also often needed to mitigate off-target toxicity. In the present study, we report a stable and efficient redox-sensitive nanoparticle system with a unique core–shell structure as a DNA carrier for cancer theranostics. Thiolated polyethylenimine (PEI-SH) is complexed with DNA through electrostatic interactions to form the core, and glycol chitosan-modified with succinimidyl 3-(2-pyridyldithio)propionate (GCS-PDP) is grafted on the surface through a thiolate-disulfide interchange reaction to form the shell. The resulting nanoparticles, GCS-PDP/PEI-SH/DNA nanoparticles (GNPs), exhibit high colloid stability in a simulated physiological environment and redox-responsive DNA release. GNPs not only show a high and redox-responsive cellular uptake, high transfection efficiency, and low cytotoxicity in vitro, but also exhibit selective tumor targeting, with minimal toxicity, in vivo, upon systemic administration. Such a performance positions GNPs as viable candidates for molecular-genetic imaging and theranostic applications.

中文翻译：

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一种独特的核壳结构、基于乙二醇壳聚糖的纳米颗粒实现了癌症选择性基因递送，并减少了脱靶效应

血清和肿瘤微环境中核酸的固有不稳定性需要合适的载体将非病毒基因递送至恶性病变。通常还需要一种赋予特异性的机制来减轻脱靶毒性。在本研究中，我们报告了一种稳定高效的氧化还原敏感纳米粒子系统，具有独特的核壳结构，可作为癌症治疗学的 DNA 载体。硫醇化聚乙烯亚胺 (PEI-SH) 通过静电相互作用与 DNA 络合形成核心，用 3-(2-吡啶基二硫代)丙酸琥珀酰亚胺酯 (GCS-PDP) 修饰的乙二醇壳聚糖通过硫醇盐-二硫键交换接枝在表面反应形成壳。得到的纳米颗粒，GCS-PDP/PEI-SH/DNA 纳米颗粒 (GNPs)，在模拟生理环境中表现出高胶体稳定性和氧化还原反应性 DNA 释放。GNPs不仅在体外表现出高和氧化还原反应性细胞摄取、高转染效率和低细胞毒性，而且在全身给药后在体内表现出选择性肿瘤靶向，毒性最小。这种性能将 GNP 定位为分子遗传成像和治疗诊断应用的可行候选者。