Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Science, Anhui University, 111 Jiu long Road, Hefei, Anhui Province 230601, PR China.
Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Science, Anhui University, 111 Jiu long Road, Hefei, Anhui Province 230601, PR China.
Int J Biol Macromol. 2019 May 15;129:477-487. doi: 10.1016/j.ijbiomac.2019.02.072. Epub 2019 Feb 13.
This work described the preparation of two type nanogels based on the crosslinking between carboxymethyl chitosan (CMCS) and two different crosslink agents, an acid-labile cyclic ortho ester compound with dual epoxy end groups (OEDe) or corresponding non-sensitive ethyleneglycol diglycidyl ether (EGDE). The particle size, zeta potential, and micromorphology were characterized by dynamic light scattering and electron microscopy, respectively. Nanogels' stability was also investigated at physiological environments. Doxorubicin hydrochloride as a therapeutic drug model was efficiently embedded into nanogels. The pH-triggered size changing, degradation and drug release were then investigated at three different pH values. Cellular uptake and cytotoxicity evaluation demonstrated that NG1/DOX could be successfully degraded and efficiently release DOX in acid cell organelles, leading to higher cytotoxicity than NG2/DOX. The accumulation and penetration of these DOX-loaded nanogel were then investigated by tumor-like multicellular spheroids (MCTS). The results indicated that the acid-degradable nanogels can deliver more DOX into the inner of MCTS by the hydrolysis of ortho ester bonds, thus efficiently inhibit the growth of MCTS. All results suggested that the acid-degradable nanogels could be degraded in mildly acidic conditions and remain stable at physiological environment, which indicated that the acid-degradable nanogels would be potentially useful as drug carriers.
本工作描述了两种纳米凝胶的制备，这两种纳米凝胶通过羧甲基壳聚糖（CMCS）与两种不同的交联剂之间的交联而形成，这两种交联剂分别是具有双环氧端基的酸敏感环原酸酯化合物（OEDe）或相应的非敏感的乙二醇二缩水甘油醚（EGDE）。通过动态光散射和电子显微镜分别对纳米凝胶的粒径、Zeta 电位和微观形态进行了表征。还在生理环境下研究了纳米凝胶的稳定性。盐酸阿霉素作为治疗药物模型被有效地嵌入纳米凝胶中。然后在三种不同的 pH 值下研究了 pH 触发的尺寸变化、降解和药物释放。细胞摄取和细胞毒性评估表明，NG1/DOX 可以在酸性细胞器中成功降解并有效地释放 DOX，从而导致比 NG2/DOX 更高的细胞毒性。然后通过肿瘤样多细胞球体（MCTS）研究了这些载药纳米凝胶的积累和渗透。结果表明，酸降解纳米凝胶可以通过原酸酯键的水解将更多的 DOX 递送到 MCTS 的内部，从而有效地抑制 MCTS 的生长。所有结果表明，酸降解纳米凝胶可以在轻度酸性条件下降解，并在生理环境中保持稳定，这表明酸降解纳米凝胶可能作为药物载体具有潜在的用途。
