f496292e0b91ba4b5da1f764c6154118 pharma_a2019v11p177.pdf 90adf7780c79e0bc27bdb6f30bd77b8418c6cfb1 pharma_a2019v11p177.pdf d8652db00c44e92fde2d8f6b7c8b4948326a50ad5e0f3250d1b2d24de1abf7ab pharma_a2019v11p177.pdf Title: Cell Internalization in Fluidic Culture Conditions Is Improved When Microparticles Are Specifically Targeted to the Human Epidermal Growth Factor Receptor 2 (HER2) Subject: Purpose: To determine if the specific targeting of microparticles improves their internalization by cells under fluidic conditions. Methods: Two isogenic breast epithelial cell lines, one overexpressing the Human Epidermal Growth Factor Receptor 2 (HER2) oncogene (D492HER2) and highly tumorigenic and the other expressing HER2 at much lower levels and non-tumorigenic (D492), were cultured in the presence of polystyrene microparticles of 1 m in diameter, biofunctionalized with either a specific anti-HER2 antibody or a non-specific secondary antibody. Mono- and cocultures of both cell lines in static and fluidic conditions were performed, and the cells with internalized microparticles were scored. Results: Globally, the D492 cell line showed a higher endocytic capacity than the D492HER2 cell line. Microparticles that were functionalized with the anti-HER2 antibody were internalized by a higher percentage of cells than microparticles functionalized with the non-specific secondary antibody. Although internalization was reduced in fluidic culture conditions in comparison with static conditions, the increase in the internalization of microparticles biofunctionalized with the anti-HER2 antibody was higher for the cell line overexpressing HER2. Conclusion: The biofunctionalization of microparticles with a specific targeting molecule remarkably increases their internalization by cells in fluidic culture conditions (simulating the blood stream). This result emphasizes the importance of targeting for future in vivo delivery of drugs and bioactive molecules through microparticles. Keywords: microfluidics; coculture; HER2; polystyrene Ps; biofunctionalization Author: Inmaculada Mora-Espí, Elena Ibáñez, Jorge Soriano, Carme Nogués, Thorarinn Gudjonsson and Leonardo Barrios Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Thu Apr 11 09:53:24 2019 CEST ModDate: Thu Apr 11 09:53:24 2019 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2497818 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- TQQKFB+URWPalladioL-Ital Type 1 Custom yes yes no 100 0 ZEBPZG+URWPalladioL-Bold Type 1 Custom yes yes no 101 0 IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 102 0 FVOKLJ+URWPalladioL-Roma Type 1 Custom yes yes no 103 0 XFIZIB+CMSY10 Type 1 Builtin yes yes no 104 0 MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 105 0 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BKIOJM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 278 0 BKIOKN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 279 0 BKIPBM+TimesNewRoman CID TrueType Identity-H yes yes yes 280 0 BKIOEM+PalatinoLinotype TrueType WinAnsi yes yes no 308 0 BKIOJM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 309 0 BKIOKN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 310 0 BKIPBM+TimesNewRoman CID TrueType Identity-H yes yes yes 311 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-02-21 05:29:31 CET RepresentationInformation: pharma_a2019v11p177.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-01-10 10:42:42 CET Size: 2497818 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: きちぴづひどちぬぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰あどはてふのっぴどはのちぬどぺちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぐはぬべびぴべひづのづぜ〴ぜ〰ぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰がどのづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづびぜ〴ぜ〰どのぜ〴ぜ〰こぴちぴどっぜ〴ぜ〰ぃはのつどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづびぜ〴ぜ〰どのぜ〴ぜ〰うぬふどつどっぜ〴ぜ〰ぃはのつどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅぶちぬふちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰きどっひはばちひぴどっぬづびぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: あどはてふのっぴどはのちぬどぺちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぐはぬべびぴべひづのづぜ〴ぜ〰ぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰がどのづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづびぜ〴ぜ〰どのぜ〴ぜ〰こぴちぴどっぜ〴ぜ〰ぃはのつどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづびぜ〴ぜ〰どのぜ〴ぜ〰うぬふどつどっぜ〴ぜ〰ぃはのつどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅぶちぬふちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰きどっひはばちひぴどっぬづびぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃづぬぬぜ〴ぜ〰がどのづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづびぜ〴ぜ〰どのぜ〴ぜ〰こぴちぴどっぜ〴ぜ〰ぃはのつどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづびぜ〴ぜ〰どのぜ〴ぜ〰うぬふどつどっぜ〴ぜ〰ぃはのつどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅぶちぬふちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰きどっひはばちひぴどっぬづびぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづびぜ〴ぜ〰どのぜ〴ぜ〰こぴちぴどっぜ〴ぜ〰ぃはのつどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづびぜ〴ぜ〰どのぜ〴ぜ〰うぬふどつどっぜ〴ぜ〰ぃはのつどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅぶちぬふちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰きどっひはばちひぴどっぬづびぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづびぜ〴ぜ〰どのぜ〴ぜ〰うぬふどつどっぜ〴ぜ〰ぃはのつどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅぶちぬふちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰きどっひはばちひぴどっぬづびぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぅぶちぬふちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰きどっひはばちひぴどっぬづびぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰きどっひはばちひぴどっぬづびぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴ぜ〰ちてぴづひぜ〴ぜ〰あどはてふのっぴどはのちぬどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰きどっひはばちひぴどっぬづびぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: きどっひはばちひぴどっぬづびぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴ぜ〰ちてぴづひぜ〴ぜ〰あどはてふのっぴどはのちぬどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰きどっひはばちひぴどっぬづびぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: きどっひはばちひぴどっぬづびぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: 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