title: Mechanistic Studies on the Self-Assembly of PLGA Patchy Particles and Their Potential Applications in Biomedical Imaging.
abstract: Currently, several challenges prevent poly(lactic-co-glycolic acid) (PLGA) particles from reaching clinical settings. Among these is a lack of understanding of the molecular mechanisms involved in the formation of these particles. We have been studying in depth the formation of patchy polymeric particles. These particles are made of PLGA and lipid-polymer functional groups. They have unique patch-core-shell structural features: hollow or solid hydrophobic cores and a patchy surface. Previously, we identified the shear stress as the most important parameter in a patchy particle's formation. Here, we investigated in detail the role of shear stress in the patchy particle's internal and external structure using an integrative experimental and computational approach. By cross-sectioning the multipatch particles, we found lipid-based structures embedded in the entire PLGA matrix, which represents a unique finding in the PLGA field. By developing novel computational fluid dynamics and molecular dynamics simulations, we found that the shear stress determines the internal structure of the patchy particles. Equally important, we discovered that these particles emit a photoacoustic (PA) signal in the optical clinical imaging window. Our results show that particles with multiple patches emit a higher PA signal than single-patch particles. This phenomenon most likely is due to the fact that multipatchy particles absorb more heat than single-patchy particles as shown by differential scanning calorimetry analysis. Furthermore, we demonstrated the use of patchy polymeric particles as photoacoustic molecular probes both in vitro and in vivo studies. The fundamental studies described here will help us to design more effective PLGA carriers for a number of medical applications as well as to accelerate their medical translation.
authors.affiliation: Bioengineering Department, George Mason University , 4400 University Drive, MS 1G5, Fairfax, Virginia 22030, United States.|Krasnow Institute for Advanced Study, George Mason University , 4400 University Drive, MS 2A1, Fairfax, Virginia 22030, United States.
authors.forename: C
authors.initials: C
authors.lastname: Salvador-Morales
authors.affiliation: Bioengineering Department, George Mason University , 4400 University Drive, MS 1G5, Fairfax, Virginia 22030, United States.|Krasnow Institute for Advanced Study, George Mason University , 4400 University Drive, MS 2A1, Fairfax, Virginia 22030, United States.
authors.forename: Binal
authors.initials: B
authors.lastname: Brahmbhatt
authors.affiliation: Center for Bioinformatics and Integrative Biology, Facultad de Ciencias Biologicas, Universidad Andres Bello , Santiago, Chile 8370146.
authors.forename: V
authors.initials: V
authors.lastname: Márquez-Miranda
authors.affiliation: Center for Bioinformatics and Integrative Biology, Facultad de Ciencias Biologicas, Universidad Andres Bello , Santiago, Chile 8370146.
authors.forename: I
authors.initials: I
authors.lastname: Araya-Duran
authors.affiliation: Fundación Fraunhofer Chile Research , M. Sanchez Fontecilla 310, Las Condes, Chile 7550296.
authors.forename: J
authors.initials: J
authors.lastname: Canan
authors.affiliation: Center for Bioinformatics and Integrative Biology, Facultad de Ciencias Biologicas, Universidad Andres Bello , Santiago, Chile 8370146.
authors.forename: F
authors.initials: F
authors.lastname: Gonzalez-Nilo
authors.affiliation: Center for Bioinformatics and Integrative Biology, Facultad de Ciencias Biologicas, Universidad Andres Bello , Santiago, Chile 8370146.|Center for Integrative Medicine and Innovative Science, Faculty of Medicine, Universidad Andres Bello , Santiago, Chile 8370146.
authors.forename: C
authors.initials: C
authors.lastname: Vilos
authors.affiliation: Bioengineering Department, George Mason University , 4400 University Drive, MS 1G5, Fairfax, Virginia 22030, United States.|Krasnow Institute for Advanced Study, George Mason University , 4400 University Drive, MS 2A1, Fairfax, Virginia 22030, United States.
authors.forename: J
authors.initials: J
authors.lastname: Cebral
authors.affiliation: Bioengineering Department, George Mason University , 4400 University Drive, MS 1G5, Fairfax, Virginia 22030, United States.|Krasnow Institute for Advanced Study, George Mason University , 4400 University Drive, MS 2A1, Fairfax, Virginia 22030, United States.
authors.forename: F
authors.initials: F
authors.lastname: Mut
authors.affiliation: Center for Computational Fluid Dynamics, College of Sciences, George Mason University , Fairfax, Virginia 22030, United States.
authors.forename: R
authors.initials: R
authors.lastname: Lohner
authors.affiliation: Center for Molecular Imaging, Department of Radiology, Virginia Commonwealth University , Richmond, Virginia 23298, United States.
authors.forename: B
authors.initials: B
authors.lastname: Leong
authors.affiliation: Center for Molecular Imaging, Department of Radiology, Virginia Commonwealth University , Richmond, Virginia 23298, United States.
authors.forename: G
authors.initials: G
authors.lastname: Sundaresan
authors.affiliation: Center for Molecular Imaging, Department of Radiology, Virginia Commonwealth University , Richmond, Virginia 23298, United States.
authors.forename: J
authors.initials: J
authors.lastname: Zweit
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015335:Molecular Probes / Q000737:chemistry* / Q000648:ultrastructure; D061088:Photoacoustic Techniques; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D033081:Shear Strength
chemical_list: D015335:Molecular Probes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid