title: Smart Cancer Cell Targeting Imaging and Drug Delivery System by Systematically Engineering Periodic Mesoporous Organosilica Nanoparticles.
abstract: The integration of diagnosis and therapy into one nanoplatform, known as theranostics, has attracted increasing attention in the biomedical areas. Herein, we first present a cancer cell targeting imaging and drug delivery system based on engineered thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The PMOs are stably and selectively conjugated with near-infrared fluorescence (NIRF) dye Cyanine 5.5 (Cy5.5) and anti-Her2 affibody on the outer surfaces to endow them with excellent NIRF imaging and cancer targeting properties. Also, taking the advantage of the thioether-group-incorporated mesopores, the release of chemotherapy drug doxorubicin (DOX) loaded in the PMOs is responsive to the tumor-related molecule glutathione (GSH). The drug release percentage reaches 84.8% in 10 mM of GSH solution within 24 h, which is more than 2-fold higher than that without GSH. In addition, the drug release also exhibits pH-responsive, which reaches 53.6% at pH 5 and 31.7% at pH 7.4 within 24 h. Confocal laser scanning microscopy and flow cytometry analysis demonstrate that the PMOs-based theranostic platforms can efficiently target to and enter Her2 positive tumor cells. Thus, the smart imaging and drug delivery nanoplatforms induce high tumor cell growth inhibition. Meanwhile, the Cy5.5 conjugated PMOs perform great NIRF imaging ability, which could monitor the intracellular distribution, delivery and release of the chemotherapy drug. In addition, cell viability and histological assessments show the engineered PMOs have good biocompatibility, further encouraging the following biomedical applications. Over all, the systemically engineered PMOs can serve as a novel cancer cell targeting imaging and drug delivery platform with NIRF imaging, GSH and pH dual-responsive drug release, and high tumor cell targeting ability.
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.|Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Nan
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health , Bethesda, Maryland 20892, United States.|Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University , Shenzhen, 518060 Guangdong, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.
authors.forename: Shouju
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.
authors.forename: Yunlei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.|State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210093 Jiangsu P.R. China.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Teng
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University , Nanjing, 210002 Jiangsu, P.R. China.|State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210093 Jiangsu P.R. China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D018613:Microscopy, Confocal; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017646:Organosilicon Compounds / Q000737:chemistry; D016062:Porosity; D013440:Sulfides / Q000737:chemistry; D000068936:Theranostic Nanomedicine
chemical_list: D000970:Antineoplastic Agents; D017646:Organosilicon Compounds; D013440:Sulfides; D004317:Doxorubicin
keywords: HER2 positive cancer; cancer cell targeting; drug delivery; near-infrared fluorescence imaging; periodic mesoporous organosilica