title: Organosilane and Polyethylene Glycol Functionalized Magnetic Mesoporous Silica Nanoparticles as Carriers for CpG Immunotherapy In Vitro and In Vivo.
abstract: Cytosine-guanine (CpG) containing oligodeoxynucleotides (ODN) have significant clinical potential as immunotherapeutics. However, limitations exist due to their transient biological stability in vivo, lack of specificity for target cells, and poor cellular uptake. To address these issues, we prepared amine magnetic mesoporous silica nanoparticles (M-MSN-A) then further modified with polyethylene glycol (PEG) for use as CpG delivery vectors. The PEG modified M-MSN-A (M-MSN-P) had notable CpG ODN loading capacity, negligible cytotoxicity, and were easily internalized into cells where they released the loaded CpG into the cytoplasm. As a result, such complexes were effective in activating macrophages and inhibiting tumor cells when combined with chemotherapeutics in vitro. Furthermore, these complexes had excellent immuno-stimulating activity in vivo, compared to the free CpG therapeutics. We report here a highly effective MSNs-based delivery system with great potential as a therapeutic CpG formulation in cancer immunotherapy.
authors.affiliation: Center for Medical Research, the Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
authors.forename: Hengrui
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Qilu Pharmaceutical Co. Ltd, Jinan, 250101, China.
authors.forename: Songsong
authors.initials: S
authors.lastname: Wen
authors.affiliation: Tong Ren Hospital Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai, 200336, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Fengxian Hospital affiliated to Southern Medical University, 6600 NanFeng Road, Shanghai, 201499, China.
authors.forename: Zhenliang
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000327:Adsorption; D000818:Animals; D001692:Biological Transport; D049109:Cell Proliferation; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D059346:Magnets / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D016062:Porosity; D000067996:RAW 264.7 Cells; D012821:Silanes / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C408982:CPG-oligonucleotide; D004337:Drug Carriers; D009838:Oligodeoxyribonucleotides; D012821:Silanes; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D012822:Silicon Dioxide