School of Chemical Engineering and Theranostic Macromolecules Research Center , Sungkyunkwan University , Suwon 16419 , Republic of Korea.
Biomacromolecules. 2018 Jun 11;19(6):2062-2070. doi: 10.1021/acs.biomac.8b00195. Epub 2018 Apr 11.
In this work, pH-responsive polypeptide-based nanogels are reported as potential drug delivery systems. By the formation of pH-sensitive benzoic imine bonds, pH-responsive nanogels are constructed using hydrophilic methoxy poly(ethylene glycol)- b-poly[ N-[ N-(2-aminoethyl)-2-aminoethyl]-l-glutamate] (MPEG- b-PNLG) and hydrophobic terephthalaldehyde (TPA) as a cross-linker. At pH 7.4, MPEG- b-PNLG nanogels exhibit high stabilities with hydrophobic inner cores, which allow encapsulation of hydrophobic therapeutic agents. Under tumoral acidic environments (pH ∼6.4), the cleavage of benzoic imine bonds induces the destruction of MPEG- b-PNLG nanogels and leads to rapid release of their payloads. The formation and pH sensitivity of the nanogels are investigated by dynamic light scattering. These nanogels exhibit excellent stabilities in the presence of salt or against dilution. The globular morphologies of the nanogels are confirmed using transmission electron microscopy. Doxorubicin is used as a model drug to evaluate drug encapsulation and release. Finally, the anticancer activities of the drug-encapsulated nanogels are assessed in vitro.
在这项工作中，报告了基于 pH 响应多肽的纳米凝胶作为潜在的药物传递系统。通过形成 pH 敏感的苯甲酰亚胺键，使用亲水性甲氧基聚（乙二醇）-b-聚[N-[N-(2-氨基乙基)-2-氨基乙基]-L-谷氨酸]（MPEG-b-PNLG）和疏水性对苯二甲醛（TPA）作为交联剂构建 pH 响应纳米凝胶。在 pH 7.4 下，MPEG-b-PNLG 纳米凝胶表现出高稳定性，具有疏水性内核，允许包封疏水性治疗剂。在肿瘤酸性环境（pH ∼6.4）下，苯甲酰亚胺键的断裂导致 MPEG-b-PNLG 纳米凝胶的破坏，并导致其有效载荷的快速释放。通过动态光散射研究了纳米凝胶的形成和 pH 敏感性。这些纳米凝胶在存在盐或稀释的情况下表现出优异的稳定性。使用透射电子显微镜证实了纳米凝胶的球形形态。阿霉素被用作模型药物来评估药物包封和释放。最后，在体外评估了载药纳米凝胶的抗癌活性。
