title: Paclitaxel-PHBV nanoparticles and their toxicity to endometrial and primary ovarian cancer cells.
abstract: This report is an integrated study to include the molecular simulation, physicochemical characterization and biological analysis of a paclitaxel-loaded PHBV nanoparticle that demonstrates uptake, release and cytotoxicity in cancer cell lines. Taking this nanoparticle one step closer to its use in a clinical setting, we demonstrate that it causes significant cell death in primary cultures of stage IIIc serous ovarian cancer cells isolated from six patients. Molecular simulations revealed a high affinity of paclitaxel for the water-polymer interface, thus the drug is delivered only when the polymer near it is degraded. The Fourier transform infrared spectroscopy suggests the formation of a short-lived crystalline phase, also observed in the CG simulations, and transmission electron microscopy revealed branched structures on the surface of particles, which disappeared after 4 days. Biological analyses indicated that these particles have a 48-h window of toxicity protection, allowing for the endocytosis of the particle by the cells; this finding was corroborated by confocal microscopy and flow cytometry. The low cost to synthesize PHBV using microorganisms and the potential chemical modifications of the polymer make it attractive for inexpensive, large-scale pharmaceutical production.
authors: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science (CIMIS), Echaurren 183, Santiago, Chile; Centro para el Desarrollo de la Nanociencia y Nanotecnología, Universidad de Santiago de Chile, Ecuador 3493, Santiago, Chile.
authors: Cristian
authors: C
authors: Vilos
authors: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science (CIMIS), Echaurren 183, Santiago, Chile.
authors: Francisco A
authors: FA
authors: Morales
authors: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science (CIMIS), Echaurren 183, Santiago, Chile.
authors: Paula A
authors: PA
authors: Solar
authors: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science (CIMIS), Echaurren 183, Santiago, Chile.
authors: Natalia S
authors: NS
authors: Herrera
authors: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Republica 239, Santiago, Chile.
authors: Fernando D
authors: FD
authors: Gonzalez-Nilo
authors: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Republica 239, Santiago, Chile.
authors: Daniel A
authors: DA
authors: Aguayo
authors: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Republica 239, Santiago, Chile.
authors: Hegaly L
authors: HL
authors: Mendoza
authors: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Republica 239, Santiago, Chile; Fundación Fraunhofer Chile Research, M. Sánchez Fontecilla 310 piso 14, Las Condes, Chile.
authors: Jeffrey
authors: J
authors: Comer
authors: Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors: Maria L
authors: ML
authors: Bravo
authors: Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors: Pamela A
authors: PA
authors: Gonzalez
authors: Facultad de Medicina, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors: Sumie
authors: S
authors: Kato
authors: Facultad de Medicina, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors: Mauricio A
authors: MA
authors: Cuello
authors: Hospital Gustavo Fricke, Alvarez 1532, Viña del Mar, Chile.
authors: Catalina
authors: C
authors: Alonso
authors: Hospital Gustavo Fricke, Alvarez 1532, Viña del Mar, Chile.
authors: Erasmo J
authors: EJ
authors: Bravo
authors: Fundación Arturo López Pérez, Rancagua 878, Santiago, Chile.
authors: Eva I
authors: EI
authors: Bustamante
authors: Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors: Gareth I
authors: GI
authors: Owen
authors: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science (CIMIS), Echaurren 183, Santiago, Chile; Centro para el Desarrollo de la Nanociencia y Nanotecnología, Universidad de Santiago de Chile, Ecuador 3493, Santiago, Chile. Electronic address: luis.velasquez@unab.cl.
authors: Luis A
authors: LA
authors: Velasquez
mesh_terms: D016923:Cell Death / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010078:Oxazines / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D010316:Particle Size; D011091:Polyesters / Q000633:toxicity*; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry; D000094122:Polyhydroxybutyrates
chemical_list: D010078:Oxazines; D017239:Paclitaxel; D011091:Polyesters; D014867:Water; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates; C044808:nile red