Sizovs Antons, McLendon Patrick M, Srinivasachari Sathya, Reineke Theresa M
Department of Chemistry, Macromolecules and Interfaces Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA
Top Curr Chem. 2010;296:131-90. doi: 10.1007/128_2010_68.
Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylenimine and polylysine and their effect on transfection and biocompatibility. Unique scaffolds, such as clusters and polymers based on cyclodextrin (CD), are also discussed, with the focus on recent successes in vivo and in the clinic. These results are presented with the emphasis on the role of carbohydrate and charge on transfection. Use of carbohydrates as molecular recognition ligands for cell-type specific delivery is also briefly reviewed. We contend that carbohydrates have contributed significantly to progress in the field of non-viral DNA delivery, and these new discoveries are impactful for developing new vehicles and materials for treatment of human disease.
碳水化合物已被研究并开发为将核酸转运到细胞中的递送载体。在本综述中，我们介绍了基于碳水化合物的聚合物载体用于核酸递送的最新进展，重点关注临床前模型在体外和体内的近期成功案例。基于天然多糖壳聚糖、透明质酸、支链淀粉、葡聚糖和裂褶菌多糖的聚合物支架各自具有独特的性质和修饰潜力，本文将重点围绕简便的合成路线以及在生物系统中的良好性能对这些结果展开讨论。这些碳水化合物中的许多已被用于开发替代类型的生物材料，用于向典型的多聚体递送核酸，本文也将对这些新型材料进行讨论。还介绍了将共聚碳水化合物纳入基于聚乙烯亚胺和聚赖氨酸的聚合物主链中的聚合物载体，以及它们对转染和生物相容性的影响。还讨论了独特的支架，如基于环糊精（CD）的簇和聚合物，重点关注其在体内和临床的近期成功案例。呈现这些结果时强调了碳水化合物和电荷在转染中的作用。还简要回顾了将碳水化合物用作细胞类型特异性递送的分子识别配体的情况。我们认为，碳水化合物对非病毒DNA递送领域的进展做出了重大贡献，这些新发现对于开发治疗人类疾病的新载体和材料具有重要意义。
