title: Biophysical and morphological effects of nanodiamond/nanoplatinum solution (DPV576) on metastatic murine breast cancer cells in vitro.
abstract: Nanoparticles have recently gained increased attention as drug delivery systems for the treatment of cancer due to their minute size and unique chemical properties. However, very few studies have tested the biophysical changes associated with nanoparticles on metastatic cancer cells at the cellular and sub-cellular scales. Here, we investigated the mechanical and morphological properties of cancer cells by measuring the changes in cell Young's Modulus using AFM, filopodial retraction (FR) by time lapse optical light microscopy imaging and filopodial disorganization by high resolution AFM imaging of cells upon treatment with nanoparticles. In the current study, nanomechanical changes in live murine metastatic breast cancer cells (4T1) post exposure to a nanodiamond/nanoplatinum mixture dispersed in aqueous solution (DPV576), were monitored. Results showed a decrease in Young's modulus at two hours post treatment with DPV576 in a dose dependent manner. Partial FR at 20 min and complete FR at 40 min were observed. Moreover, analysis of the retraction distance (in microns) measured over time (minutes), showed that a DPV576 concentration of 15%v/v yielded the highest FR rate. In addition, DPV576 treated cells showed early signs of filopodial disorganization and disintegration. This study demonstrates the changes in cell stiffness and tracks early structural alterations of metastatic breast cancer cells post treatment with DPV576, which may have important implications in the role of nanodiamond/nanoplatinum based cancer cell therapy and sensitization to chemotherapy drugs.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA.
authors.forename: Alia
authors.initials: A
authors.lastname: Ghoneum
authors.forename: Huanqi
authors.initials: H
authors.lastname: Zhu
authors.forename: JungReem
authors.initials: J
authors.lastname: Woo
authors.forename: Nikita
authors.initials: N
authors.lastname: Zabinyakov
authors.forename: Shivani
authors.initials: S
authors.lastname: Sharma
authors.forename: James K
authors.initials: JK
authors.lastname: Gimzewski
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D045744:Cell Line, Tumor; D018130:Diamond; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D010316:Particle Size; D010984:Platinum; D011554:Pseudopodia / Q000473:pathology / Q000502:physiology
chemical_list: D004337:Drug Carriers; D010984:Platinum; D018130:Diamond