College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China; MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei, Anhui 230012, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, Anhui 230012, China.
College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China; Key Laboratory of Molecular Biology (Brain diseases), Anhui University of Chinese Medicine, Hefei, Anhui 230012, China.
Eur J Pharm Sci. 2024 Jan 1;192:106641. doi: 10.1016/j.ejps.2023.106641. Epub 2023 Nov 14.
Drug Delivery System was constructed using dopamine-coated organic-inorganic hybrid hollow mesoporous organic silica nanoparticles (HMON-PDA) as drug carriers and salvianolic acid B (SAB) as a model drug. Then, we further investigated whether it can inhibit lung metastasis of breast cancer by inhibiting cancer-associated fibroblasts (CAFs).
The organic-inorganic hybrid hollow mesoporous organic silica nanoparticles (HMON) were prepared. The particle size, zeta potential, and polydispersion coefficient were characterized. High-performance liquid chromatography was used to determine the effect of different feed ratios of HMON and SAB on drug loading rate. Then, SAB-loaded HMON were modified by polydopamine, which is called SAB@HMON-PDA. Cell viability was detected by MTT assay. The migration of 4T1 cells was investigated by wound healing experiment, and the invasion of 4T1 cells was detected by the transwell method. Finally, the mouse breast cancer lung metastasis models were used to explore whether SAB@HMON-PDA can inhibit lung metastasis of breast cancer by inhibiting CAFs.
The obtained nanoparticles have hollow spherical structure. The average particle sizes of HMON, SAB@HMON, and SAB@HMON-PDA were 143.5 ± 0.03, 138.3 ± 0.02, and 172.3 ± 0.18 nm, respectively. The zeta potentials were -44.33±0.15, -41.4 ± 1.30, and -24.13±0.47 mV, respectively. When the ratio of HMON to SAB was 2:1, the drug loading rate reached (18.37±0.04)%. In addition, the prepared SAB@HMON-PDA responded to release SAB under acidic and GSH conditions. The prepared SAB@HMON-PDA could inhibit the migration and invasion of 4T1 cells. The results showed that SAB@HMON-PDA and SAB could inhibit lung metastasis of breast cancer in mice, and SAB@HMON-PDA had a more significant inhibitory effect than SAB.
We successfully prepared SAB@HMON-PDA with the dual response of pH and GSH. SAB@HMON-PDA can inhibit the migration and invasion of 4T1 cells, and the effect is more significant than free SAB. This inhibitory effect may be related to the inhibition of CAFs. In vivo experiments demonstrated that SAB@HMON-PDA can inhibit lung metastasis of breast cancer by inhibiting CAFs, and its effect was more significant than that of free SAB.
采用多巴胺包覆的有机-无机杂化中空介孔有机硅纳米粒子（HMON-PDA）作为药物载体，以丹酚酸 B（SAB）为模型药物，构建药物传递系统。进一步研究其是否通过抑制癌相关成纤维细胞（CAFs）来抑制乳腺癌的肺转移。
制备有机-无机杂化中空介孔有机硅纳米粒子（HMON）。对其粒径、Zeta 电位和多分散系数进行了表征。采用高效液相色谱法测定 HMON 与 SAB 的不同进料比对载药率的影响。然后，用聚多巴胺对载 SAB 的 HMON 进行修饰，得到 SAB@HMON-PDA。采用 MTT 法检测细胞活力。通过划痕实验研究 4T1 细胞的迁移，通过 Transwell 法检测 4T1 细胞的侵袭。最后，利用小鼠乳腺癌肺转移模型，探讨 SAB@HMON-PDA 是否通过抑制 CAFs 来抑制乳腺癌的肺转移。
所得纳米粒子具有中空球形结构。HMON、SAB@HMON 和 SAB@HMON-PDA 的平均粒径分别为 143.5±0.03、138.3±0.02 和 172.3±0.18nm。Zeta 电位分别为-44.33±0.15、-41.4±1.30 和-24.13±0.47mV。当 HMON 与 SAB 的比例为 2:1 时，载药率达到（18.37±0.04）%。此外，所制备的 SAB@HMON-PDA 在酸性和 GSH 条件下能够响应释放 SAB。制备的 SAB@HMON-PDA 可以抑制 4T1 细胞的迁移和侵袭。结果表明，SAB@HMON-PDA 和 SAB 可以抑制小鼠乳腺癌的肺转移，并且 SAB@HMON-PDA 的抑制作用强于 SAB。
我们成功制备了具有 pH 和 GSH 双重响应的 SAB@HMON-PDA。SAB@HMON-PDA 可以抑制 4T1 细胞的迁移和侵袭，其作用强于游离 SAB。这种抑制作用可能与抑制 CAFs 有关。体内实验表明，SAB@HMON-PDA 通过抑制 CAFs 抑制乳腺癌的肺转移，其作用强于游离 SAB。
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