title: Enhanced in vivo antitumor efficacy of doxorubicin encapsulated within laponite nanodisks.
abstract: Development of various nanoscale drug carriers for enhanced antitumor therapy still remains a great challenge. In this study, laponite (LAP) nanodisks encapsulated with anticancer drug doxorubicin (DOX) at an exceptionally high loading efficiency (98.3 ± 0.77%) were used for tumor therapy applications. The long-term in vivo antitumor efficacy and toxicology of the prepared LAP/DOX complexes were analyzed using a tumor-bearing mouse model. Long-term tumor appearance, normalized tumor volume, CD31 staining, and hematoxylin and eosin (H&E)-stained tumor sections were used to evaluate the tumor therapy efficacy, while long-term animal body weight changes and H&E-stained tissue sections of different major organs were used to evaluate the toxicology of LAP/DOX complexes. Finally, the in vivo biodistribution of magnesium ions and DOX in different organs was analyzed. We showed that under the same DOX concentration, LAP/DOX complexes displayed enhanced tumor inhibition efficacy and afforded the treated mice with dramatically prolonged survival time. In vivo biodistribution data revealed that the reticuloendothelial systems (especially liver) had significantly higher magnesium uptake than other major organs, and the LAP carrier was able to be cleared out of the body at 45 days post treatment. Furthermore, LAP/DOX afforded a higher DOX uptake in the tumor region than free DOX, presumably due to the known enhanced permeability and retention effect. The developed LAP-based drug delivery system with an exceptionally high DOX payload, enhanced in vivo antitumor efficacy, and low systemic toxicity may be used as a promising platform for enhanced tumor therapy.
authors.affiliation: Department of Orthopaedics, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200080, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Shige
authors.initials: S
authors.lastname: Wang
authors.forename: Shihui
authors.initials: S
authors.lastname: Wen
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Tang
authors.forename: Jipeng
authors.initials: J
authors.lastname: Li
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017640:Silicates / Q000737:chemistry*; D016019:Survival Analysis; D014018:Tissue Distribution / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017640:Silicates; D004317:Doxorubicin; C524813:laponite