title: Nanosomes carrying doxorubicin exhibit potent anticancer activity against human lung cancer cells.
abstract: Successful chemotherapeutic intervention for management of lung cancer requires an efficient drug delivery system. Gold nanoparticles (GNPs) can incorporate various therapeutics; however, GNPs have limitations as drug carriers. Nano-sized cellular vesicles like exosomes (Exo) can ferry GNP-therapeutic complexes without causing any particle aggregation or immune response. In the present study, we describe the development and testing of a novel Exo-GNP-based therapeutic delivery system -'nanosomes'- for lung cancer therapy. This system consists of GNPs conjugated to anticancer drug doxorubicin (Dox) by a pH-cleavable bond that is physically loaded onto the exosomes (Exo-GNP-Dox). The therapeutic efficacy of Dox in nanosomes was assessed in H1299 and A549 non-small cell lung cancer cells, normal MRC9 lung fibroblasts, and Dox-sensitive human coronary artery smooth muscle cells (HCASM). The enhanced rate of drug release under acidic conditions, successful uptake of the nanosomes by the recipient cells and the cell viability assays demonstrated that nanosomes exhibit preferential cytotoxicity towards cancer cells and have minimal activity on non-cancerous cells. Finally, the underlying mechanism of cytotoxicity involved ROS-mediated DNA damage. Results from this study mark the establishment of an amenable drug delivery vehicle and highlight the advantages of a natural drug carrier that demonstrates reduced cellular toxicity and efficient delivery of therapeutics to cancer cells.
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Akhil
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Narsireddy
authors.initials: N
authors.lastname: Amreddy
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Anish
authors.initials: A
authors.lastname: Babu
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Janani
authors.initials: J
authors.lastname: Panneerselvam
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Meghna
authors.initials: M
authors.lastname: Mehta
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Ranganayaki
authors.initials: R
authors.lastname: Muralidharan
authors.affiliation: Department of Epidemiology and Statistics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Allshine
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Statistics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Yan Daniel
authors.initials: YD
authors.lastname: Zhao
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Razaq
authors.affiliation: Boone Pickens School of Geology, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Natascha
authors.initials: N
authors.lastname: Riedinger
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Hogyoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Biology, University of Oklahoma, Norman, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biology, University of Oklahoma, Norman, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Si
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Asim B
authors.initials: AB
authors.lastname: Abdel-Mageed
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Anupama
authors.initials: A
authors.lastname: Munshi
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Graduate Program in Biomedical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Ramesh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003331:Coronary Vessels / Q000473:pathology; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004789:Enzyme Activation / Q000187:drug effects; D055354:Exosomes / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D053453:Caspase 9