School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, PR China.
Wenzhou Institute of Biomaterials and Engineering, CNITECH, CAS, Wenzhou, Zhejiang Province, 325001, PR China; Engineering Research Center of Clinical Functional Materials and Diagnosis&Treatment Devices of Zhejiang Province, Wenzhou Institute of Biomaterials and Engineering, CAS, Wenzhou, Zhejiang Province, 325001, PR China.
Colloids Surf B Biointerfaces. 2019 May 1;177:178-187. doi: 10.1016/j.colsurfb.2019.01.061. Epub 2019 Jan 31.
Constructing intracellular degradable drug delivery vehicles is critical to fully exert the function of loaded drugs. Considering the poly (amino acid) is sensitively degradable to acid and enzyme which indwell in the mature lysosome, we here presented the poly(amino acid) capsules constructed by the synthetic poly(amino acid), (poly-glutamic acid, PGA and poly-ornithine, POR). The fabrication of Dox loaded poly (amino acid) capsules was demonstrated, and was thoroughly characterized by various techniques, including Zetasizer, SEM, TEM, fluorescent microscopy, and confocal laser scan microscopy. By controlling fabrication process, we tuned the carriers with different physical properties (charges and stiffness). Then, we thoroughly investigated the effects of these properties on the intracellular uptake and anti-cancer abilities of various carriers@Dox. In addition, the degradability of poly(amino acid) capsules was studied to reveal the release profiles of the carriers with or without templates from the side aspect. We found the positively charged and stiffer carriers mainly contributed to the cellular uptake process and amount, while both the uptake amount and degradability of the endocytosed carriers@Dox played a critical role on the cytotoxicity. We believe the findings here could pave the way for designing poly(amino acid) capsules or other degradable polymers based on poly(amino acid) as the drug delivery vehicles.
构建细胞内可降解的药物递送载体对于充分发挥所载药物的功能至关重要。考虑到聚(氨基酸)对驻留在成熟溶酶体中的酸和酶敏感降解,我们在此展示了由合成聚(氨基酸)(聚谷氨酸,PGA 和聚鸟氨酸,POR)构建的聚(氨基酸)胶囊。我们演示了载多柔比星的聚(氨基酸)胶囊的制备,并通过各种技术对其进行了彻底的表征,包括 Zetasizer、SEM、TEM、荧光显微镜和共聚焦激光扫描显微镜。通过控制制备工艺,我们可以调整载体的物理性质(电荷和刚性)。然后,我们深入研究了这些性质对各种载体@多柔比星的细胞内摄取和抗癌能力的影响。此外,还研究了聚(氨基酸)胶囊的降解性,以从侧面揭示有无模板的载体的释放情况。我们发现带正电荷和刚性较强的载体主要有助于细胞摄取过程和数量,而内吞的载体@多柔比星的摄取量和降解性对细胞毒性起着关键作用。我们相信这里的发现可以为设计基于聚(氨基酸)的聚(氨基酸)胶囊或其他可降解聚合物作为药物递送载体铺平道路。