title: Enzyme responsive drug delivery system based on mesoporous silica nanoparticles for tumor therapy in vivo.
abstract: To reduce the toxic side effects of traditional chemotherapeutics in vivo, we designed and constructed a biocompatible, matrix metalloproteinases (MMPs) responsive drug delivery system based on mesoporous silica nanoparticles (MSNs). MMPs substrate peptide containing PLGLAR (sensitive to MMPs) was immobilized onto the surfaces of amino-functionalized MSNs via an amidation reaction, serving as MMPs sensitive intermediate linker. Bovine serum albumin was then covalently coupled to linker as end-cap for sealing the mesopores of MSNs. Lactobionic acid was further conjugated to the system as targeting motif. Doxorubicin hydrochloride was used as the model anticancer drug in this study. A series of characterizations revealed that the system was successfully constructed. The peptide-functionalized MSNs system demonstrated relatively high sensitivity to MMPs for triggering drug delivery, which was potentially important for tumor therapy since the tumor's microenvironment overexpressed MMPs in nature. The in vivo experiments proved that the system could efficiently inhibit the tumor growth with minimal side effects. This study provides an approach for the development of the next generation of nanotherapeutics toward efficient cancer treatment.
authors: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China. Research Center for Medicine and Biology, Zunyi Medical University, Zunyi 563003, People's Republic of China.
authors: Yun
authors: Y
authors: Liu
authors: Xingwei
authors: X
authors: Ding
authors: Jinghua
authors: J
authors: Li
authors: Zhong
authors: Z
authors: Luo
authors: Yan
authors: Y
authors: Hu
authors: Junjie
authors: J
authors: Liu
authors: Liangliang
authors: L
authors: Dai
authors: Jun
authors: J
authors: Zhou
authors: Changjun
authors: C
authors: Hou
authors: Kaiyong
authors: K
authors: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology; D012822:Silicon Dioxide / Q000737:chemistry*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012822:Silicon Dioxide; D004317:Doxorubicin; D020782:Matrix Metalloproteinases