ec3320a1eaea8a2e9db1b3c979dfb45d pmc_32075316.pdf 9833f22ebe7e5f39fe66ea63d6d904ab037c64d7 pmc_32075316.pdf 075abc0a93d9fe17e9c64c08478f78b6a6001f915ae23c04e560a4b7be4abdf7 pmc_32075316.pdf Title: The Biological Potential Hidden in Inclusion Bodies Subject: Inclusion bodies (IBs) are protein nanoclusters obtained during recombinant protein production processes, and several studies have demonstrated their potential as biomaterials for therapeutic protein delivery. Nevertheless, IBs have been, so far, exclusively sifted by their biological activity in vitro to be considered in further protein-based treatments in vivo. Matrix metalloproteinase-9 (MMP-9) protein, which has an important role facilitating the migration of immune cells, was used as model protein. The MMP-9 IBs were compared with their soluble counterpart and with MMP-9 encapsulated in polymeric-based micelles (PM) through ionic and covalent binding. The soluble MMP-9 and the MMP-9-ionic PM showed the highest activity values in vitro. IBs showed the lowest activity values in vitro, but the specific activity evolution in 50% bovine serum at room temperature proved that they were the most stable format. The data obtained with the use of an air-pouch mouse model showed that MMP-9 IBs presented the highest in vivo activity compared to the soluble MMP-9, which was associated only to a low and a transitory peak of activity. These results demonstrated that the in vivo performance is the addition of many parameters that did not always correlate with the in vitro behavior of the protein of interest, becoming especially relevant at evaluating the potential of IBs as a protein-based nanomaterial for therapeutic purposes. Keywords: inclusion body; polymeric micelle; stability; matrix metalloproteinase-9; in vitro; in vivo Author: Laia Gifre-Renom, Joaquin Seras-Franzoso, Diana Rafael, Fernanda Andrade, Olivia Cano-Garrido, Francesc Martinez-Trucharte, Estefania Ugarte-Berzal, Erik Martens, Lise Boon, Antonio Villaverde, Ghislain Opdenakker, Simó Schwartz Jr., Anna Arís and Elena Garcia-Fruitós Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Sat Feb 15 11:45:00 2020 CET ModDate: Sat Feb 15 11:45:00 2020 CET Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3069216 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- TGLUQF+URWPalladioL-Ital Type 1 Custom yes yes no 115 0 SSKEQJ+URWPalladioL-Bold Type 1 Custom yes yes 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ききぐ〭〹〠がはちつどので〠ぅててどっちっべ〠 Item: Title: じ〭ひちべ〠ぐとはぴはづぬづっぴひはの〠こばづっぴひはびっはばべ〠〨じぐこ〩〠 Item: Title: ぐひはぴづどの〠こぴちぢどぬどぴべ〠ぁびびちべ〠 Item: Title: ぉの〠ざどぶは〠ぃはねばちひどびはの〠はて〠ぴとづ〠ぉのてぬちねねちぴはひべ〠げづびばはのびづ〠ぴは〠こはぬふぢどぬどぺづつ〠ききぐ〭〹〠ぶづひびふび〠ききぐ〭〹〠ぉあび〬〠さびどので〠ち〠きはふびづ〠きはつづぬ〠 Item: Title: こぴちぴどびぴどっちぬ〠ぁのちぬべびどび〠 Item: Title: げづびふぬぴび〠 Children: Item: Title: ぁっぴどぶどぴべ〠はて〠ききぐ〭〹〠ぎちのはばちひぴどっぬづび〠 Item: Title: ぉの〠ざどぴひは〠ききぐ〭〹〠こぴちぢどぬどぴべ〠 Item: Title: ぉの〠ざどぶは〠ききぐ〭〹〠ぁっぴどぶどぴべ〠 Item: Title: いどびっふびびどはの〠 Item: Title: ぃはのっぬふびどはのび〠 Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: TGLUQF+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: TGLUQF+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: YICMPF+Rpcxr FontSubset: true FirstChar: 151 LastChar: 174 FontDescriptor: FontName: YICMPF+Rpcxr Flags: Symbolic FontBBox: -212, -286, 1344, 973 FontFile: true Font: BaseFont: 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