title: Tumor-Homing Cell-Penetrating Peptide Linked to Colloidal Mesoporous Silica Encapsulated (-)-Epigallocatechin-3-gallate as Drug Delivery System for Breast Cancer Therapy in Vivo.
abstract: Chemotherapy is the use of chemical drugs to prevent cancer cell proliferation, invasion, and metastasis, but a serious obstacle is that chemotherapeutics strikes not only on cancerous cells, but also on normal cells. Thus, anticancer drugs without side effects should be developed and extracted. (-)-Epigallocatechin-3-gallate (EGCG), a major ingredient of green tea, possesses excellent medicinal values, such as anticancer effects, DNA-protective effects, etc. However, EGCG will be mostly metabolized if it is directly orally ingested. Here, we report a drug delivery system (DDS) for loading EGCG to enhance its stability, promising target and anticancer effects in vitro and in vivo. The designed DDS is composed of three main moieties: anticancer drug, EGCG; drug vector, colloidal mesoporous silica (CMS); target ligand, breast tumor-homing cell-penetrating peptide (PEGA-pVEC peptide). Based on the results of CCK-8 assay, confocal imaging, cell cycle analysis, and Western blot, the anticancer effect of EGCG was increased by loading of EGCG into CMS and CMS@peptide. In vivo treatment displayed that CMS had a not obvious influence on breast tumor bearing mice, but CMS@peptide@EGCG showed the greatest tumor inhibition rate, with about 89.66%. H&E staining of organs showed no tissue injury in all experimental groups. All the above results prove that EGCG is an excellent anticancer drug without side effects and CMS@peptide could greatly promote the efficacy of EGCG on breast tumors by targeted accumulation and release, which provide much evidence for the CMS@peptide as a promising and targeting vector for DDS.
authors.affiliation: †China-America Cancer Research Institute, Guangdong Medical University, Dongguan, Guangdong 523808, China.|∥State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation of Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: ‡Department of Pathology, Ganzhou Health School, Ganzhou, Jiangxi 341000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.affiliation: ∥State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation of Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xue
authors.affiliation: §Institute of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: #Experimental Animal Center, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Bao
authors.affiliation: ∥State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation of Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: ∥State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation of Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors.forename: Jun-jie
authors.initials: JJ
authors.lastname: Zhu
authors.affiliation: †China-America Cancer Research Institute, Guangdong Medical University, Dongguan, Guangdong 523808, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D016062:Porosity; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D002392:Catechin; C045651:epigallocatechin gallate
keywords: (-)-epigallocatechin-3-gallate; PEGA-pVEC peptide; colloidal mesoporous silica; drug delivery system; targeted therapy