title: Synthesis of polymer-lipid nanoparticles for image-guided delivery of dual modality therapy.
abstract: For advanced treatment of diseases such as cancer, multicomponent, multifunctional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly(lactic-co-glycolic) acid (PLGA) polymer is formulated into a polymer-lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near-infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics-based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine-tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near-infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging.
authors: Translational and Molecular Imaging Institute and Imaging Science Laboratories and ⊥Zena and Michael and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, New York, New York 10029, United States.
authors: Aneta J
authors: AJ
authors: Mieszawska
authors: YongTae
authors: Y
authors: Kim
authors: Anita
authors: A
authors: Gianella
authors: Inge
authors: I
authors: van Rooy
authors: Bram
authors: B
authors: Priem
authors: Matthew P
authors: MP
authors: Labarre
authors: Canturk
authors: C
authors: Ozcan
authors: David P
authors: DP
authors: Cormode
authors: Artiom
authors: A
authors: Petrov
authors: Robert
authors: R
authors: Langer
authors: Omid C
authors: OC
authors: Farokhzad
authors: Zahi A
authors: ZA
authors: Fayad
authors: Willem J M
authors: WJ
authors: Mulder
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D061848:Optical Imaging / Q000379:methods; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000077157:Sorafenib
chemical_list: D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D010671:Phenylurea Compounds; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D009536:Niacinamide; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin; D000077157:Sorafenib
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