Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.
Tongji Hospital, Tongji University, Shanghai, People's Republic of China.
IET Nanobiotechnol. 2018 Jun;12(4):446-452. doi: 10.1049/iet-nbt.2017.0100.
In this study, a promising drug nano-carrier system consisting of mono-dispersed and pH sensitive carboxylated chitosan-hollow mesoporous silica nanoparticles (Ccs-HMSNs) suitable for the treatment of malignant cells was synthesised and investigated. At neutral pH, the Ccs molecules are orderly aggregated state, which could effectively hinder the release of loaded drug molecules. However, in slightly acidic environment, Ccs chains are heavily and flexibly entangled in gel state, which would enhance the subsequent controlled release of the loaded drug. Using doxorubicin hydrochloride (DOX•HCl) as the drug model, their results demonstrated that the system had an excellent loading efficiency (64.74 μg/mg Ccs-HMSNs) and exhibited a pH-sensitive release behaviour. Furthermore, confocal laser scanning microscopy revealed that the Ccs-HMSNs nanocomposite could effectively deliver and release DOX•HCl to the nucleus of HeLa cells, thereby inducing apoptosis. In addition, MTT assay also confirmed that DOX•HCl loaded Ccs-HMSNs (DOX•HCl@Ccs-HMSNs) exhibited a good anticancer effect on HeLa cells with a time-dependent manner. Finally, haemolysis experiment showed Ccs-HMSNs had no haemolytic activity at all the tested concentrations (5-320 μg/mL). Thus, this biocompatible and effective nano-carrier system will have potential applications in controllable drug delivery and cancer therapy.
在这项研究中,合成并研究了一种由单分散且 pH 敏感的羧化壳聚糖-中空介孔硅纳米粒子(Ccs-HMSNs)组成的有前途的药物纳米载体系统,适用于治疗恶性细胞。在中性 pH 下,Ccs 分子处于有序聚集状态,可有效阻止所载药物分子的释放。然而,在略微酸性的环境中,Ccs 链在凝胶状态下严重且灵活地缠结,从而增强随后对所载药物的控制释放。以盐酸阿霉素(DOX•HCl)为药物模型,结果表明该系统具有出色的载药效率(64.74μg/mg Ccs-HMSNs),并表现出 pH 敏感的释放行为。此外,共聚焦激光扫描显微镜显示,Ccs-HMSNs 纳米复合材料可有效将 DOX•HCl 递送至 HeLa 细胞的核内,从而诱导细胞凋亡。此外,MTT 测定也证实,载有 DOX•HCl 的 Ccs-HMSNs(DOX•HCl@Ccs-HMSNs)对 HeLa 细胞具有良好的抗癌作用,且具有时间依赖性。最后,溶血实验表明,在所有测试浓度(5-320μg/mL)下,Ccs-HMSNs 均无溶血活性。因此,这种具有生物相容性和有效性的纳米载体系统将在可控药物输送和癌症治疗方面具有潜在的应用。