title: Nuclear mapping of nanodrug delivery systems in dynamic cellular environments.
abstract: Nanoformulations have shown great promise for delivering chemotherapeutics and hold tremendous clinical relevance. However nuclear mapping of the chemodrugs is important to predict the success of the nanoformulation. In this study fluorescence microscopy and a subcellular tracking algorithm were used to map the diffusion of chemotherapeutic drugs in cancer cells. Positively charged nanoparticles efficiently carried the chemodrug across the cell membrane. The algorithm helped map free drug and drug-loaded nanoparticles, revealing a varying nuclear diffusion pattern of the chemotherapeutics in drug-sensitive and -resistant cells in a live dynamic cellular environment. While the drug-sensitive cells showed an exponential uptake of the drug with time, resistant cells showed random and asymmetric drug distribution. Moreover nanoparticles carrying the drug remained in the perinuclear region, while the drug accumulated in the cell nuclei. The tracking approach has enabled us to predict the therapeutic success of different nanoscale formulations of doxorubicin.
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Ashwinkumar A
authors.initials: AA
authors.lastname: Bhirde
authors.forename: Ankur
authors.initials: A
authors.lastname: Kapoor
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Ramiro
authors.initials: R
authors.lastname: Iglesias-Bartolome
authors.forename: Albert
authors.initials: A
authors.lastname: Jin
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhang
authors.forename: Ruijun
authors.initials: R
authors.lastname: Xing
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Richard D
authors.initials: RD
authors.lastname: Leapman
authors.forename: J Silvio
authors.initials: JS
authors.lastname: Gutkind
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000465:Algorithms; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods; D053769:Nanocapsules / Q000648:ultrastructure*; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D010363:Pattern Recognition, Automated / Q000379:methods*
chemical_list: D053769:Nanocapsules; D004317:Doxorubicin