title: Improving the Anticancer Efficacy of Laminin Receptor-Specific Therapeutic Ruthenium Nanoparticles (RuBB-Loaded EGCG-RuNPs) via ROS-Dependent Apoptosis in SMMC-7721 Cells.
abstract: Functionalization can promote the uptake of nanoparticles into cancer cells via receptor-mediated endocytosis, enabling them to exert their therapeutic effects. In this paper, epigallocatechin gallate (EGCG), which has a high binding affinity to 67 kDa laminin receptor (67LR) overexpressed in HCC cells, was employed in the present study to functionalized ruthenium nanoparticles (RuNPs) loaded with luminescent ruthenium complexes to achieve antiliver cancer efficacy. [Ru(bpy)2(4-B)] (ClO4)2·2H2O (RuBB)-loaded EGCG-RuNPs (bpy = 2,2'-bipyridine) showed small particle size with narrow distribution, better stability, and high selectivity between liver cancer and normal cells. The internalization of RuBB-loaded EGCG-RuNPs was inhibited by 67LR-blocking antibody or laminin, suggesting that 67LR-mediated endocytosis played an important role in the uptake into HCC cells. Moreover, transmission electron microscopy and confocal microscopic images showed that RuBB-loaded EGCG-RuNPs accumulated in the cytoplasm of SMMC-7721 cells. Furthermore, our results indicated that the EGCG-functionalized nanoparticles displayed enhanced anticancer effects in a target-specific manner. Concentrations of RuBB-loaded EGCG-RuNPs, nontoxic in normal L-02 cells, showed direct reactive oxygen species-dependent cytotoxic, pro-apoptotic, and anti-invasive effects in SMMC-7721 cells. Furthermore, in vivo animal study demonstrated that RuBB-loaded EGCG-RuNPs possessed high antitumor efficacy on tumor-bearing nude mice. It is encouraging to conclude that the multifunctional RuNPs may form the basis of new strategies on the treatment of liver cancer and other malignancies.
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Dhairya
authors.initials: D
authors.lastname: Bhavsar
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Licong
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Qingchang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Lanmei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002392:Catechin; D002460:Cell Line; D006801:Humans; D053768:Metal Nanoparticles; D051379:Mice; D008819:Mice, Nude; D017382:Reactive Oxygen Species; D017474:Receptors, Laminin; D012428:Ruthenium
chemical_list: D017382:Reactive Oxygen Species; D017474:Receptors, Laminin; D012428:Ruthenium; D002392:Catechin
keywords: 67LR receptors; cellular targeting; fluorescence imaging; reactive oxygen species; ruthenium nanoparticles