A Unique Core-Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects.
A Unique Core-Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects.
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DOI：
10.3390/pharmaceutics14020373
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发表时间：
2022-02-07
期刊：
影响因子：
5.4
通讯作者：
Pomper MG
中科院分区：
文献类型：
--
作者：
Cheng B;Ahn HH;Nam H;Jiang Z;Gao FJ;Minn I;Pomper MG
核酸在血清和肿瘤微环境中的固有不稳定性需要一种合适的载体来将非病毒基因传递到恶性病变。通常还需要特异性赋予机制来减轻脱靶毒性。在本研究中，我们报道了一种稳定高效的氧化还原敏感纳米颗粒系统，其独特的核壳结构作为癌症治疗的DNA载体。巯基化聚乙烯亚胺（PEI-SH）通过静电作用与DNA络合形成核，经3-（2-吡啶基二硫代）丙酸琥珀酰亚胺修饰的乙二醇壳聚糖（GCS-PDP）通过巯基-二硫交换反应接枝在表面形成壳。所得纳米粒子GCS-PDP/PEI-SH/DNA纳米粒子（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的氧化还原反应性细胞摄取、高转染效率和低细胞毒性，而且在体内系统给药时也表现出选择性肿瘤靶向性，毒性最小。这样的性能使GNPs成为分子遗传成像和治疗应用的可行候选者。
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.
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影响因子：
46.2
作者：
Karimi M;Ghasemi A;Sahandi Zangabad P;Rahighi R;Moosavi Basri SM;Mirshekari H;Amiri M;Shafaei Pishabad Z;Aslani A;Bozorgomid M;Ghosh D;Beyzavi A;Vaseghi A;Aref AR;Haghani L;Bahrami S;Hamblin MR
通讯作者：
Hamblin MR
影响因子：
11.2
作者：
Jorgenson TC;Zhong W;Oberley TD
通讯作者：
Oberley TD
DOI：
10.1016/j.bbamcr.2012.06.019
发表时间：
2012-10
影响因子：
5.1
作者：
Circu, Magdalena L.;Aw, Tak Yee
通讯作者：
Aw, Tak Yee
影响因子：
4
作者：
Dillekas, Hanna;Rogers, Michael S.;Straume, Oddhjorn
通讯作者：
Straume, Oddhjorn
影响因子：
4.6
作者：
Ahn HH;Carrington C;Hu Y;Liu HW;Ng C;Nam H;Park A;Stace C;West W;Mao HQ;Pomper MG;Ullman CG;Minn I
通讯作者：
Minn I