0438d0661f70a17530425d3a5f2be124 pmc_10095016.pdf 883dd7b779f3869f563db112f28df5488c725615 pmc_10095016.pdf 986fa5cf1fd306ae54e6eb5e3dbcc9b2781b87175671feb87ce3ce22bdb34908 pmc_10095016.pdf Title: Development of New Targeted Nanotherapy Combined with Magneto-Fluorescent Nanoparticles against Colorectal Cancer Subject: The need for non-invasive therapies capable of conserving drug efficiency and stability while having specific targetability against colorectal cancer (CRC), has made nanoparticles preferable vehicles and principal building blocks for the development of complex and multi-action anti-tumoral approaches. For that purpose, we herein report the production of a combinatory anti-tumoral nanotherapy using the production of a new targeting towards CRC lines. To do so, Magneto-fluorescent NANO3 nanoparticles were used as nanocarriers for a combination of the drugs doxorubicin (DOX) and ofloxacin (OFLO). NANO3 nanoparticles’ surface was modified with two different targeting agents, a newly synthesized (anti-CA IX acetazolamide derivative (AZM-SH)) and a commercially available (anti-epidermal growth factor receptor (EGFR), Cetuximab). The cytotoxicity revealed that only DOX-containing nanosystems showed significant and even competitive cytotoxicity when compared to that of free DOX. Interestingly, surface modification with AZM-SH promoted an increased cellular uptake in the HCT116 cell line, surpassing even those functionalized with Cetuximab. The results show that the new target has high potential to be used as a nanotherapy agent for CRC cells, surpassing commercial targets. As a proof-of-concept, an oral administration form of NANO3 systems was successfully combined with Eudragit® enteric coating and studied under extreme conditions. Keywords: target nanocarriers; oral formulations; colorectal cancer; target drug delivery; targeted anticancer therapy Author: Gonçalo A. Marcelo, David Montpeyó, Joana Galhano, Ramón Martínez-Máñez, José Luis Capelo-Martínez, Julia Lorenzo, Carlos Lodeiro and Elisabete Oliveira Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Apr 1 10:26:24 2023 CEST ModDate: Sat Apr 1 10:32:54 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 23 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4819351 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 DXLCEX+VnURWPalladioL Type 1 Custom yes yes no 15 0 OBVLTG+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 FSCZYZ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 OZWELY+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 46 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 JDCKWC+CMSY10 Type 1 Builtin yes yes no 71 0 CWRMNO+EURM10 Type 1 Builtin yes yes no 81 0 NLNADN+Arial,Bold CID TrueType Identity-H yes yes yes 92 0 NLMOHA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 98 0 NLMOHC+PalatinoLinotype TrueType WinAnsi yes yes no 101 0 NLMOHE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 104 0 NLNAAM+Arial CID TrueType Identity-H yes yes yes 107 0 NLNACN+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 113 0 NLMOHA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 123 0 NLMOHB+PalatinoLinotype CID TrueType Identity-H yes yes yes 126 0 NLMOHC+PalatinoLinotype TrueType WinAnsi yes yes no 132 0 NLMOHE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 135 0 NLNACN+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 138 0 NLMOHA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 152 0 NLMOHC+PalatinoLinotype TrueType WinAnsi yes yes no 155 0 NLMOHE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 158 0 NLMOHA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 172 0 NLMOHC+PalatinoLinotype TrueType WinAnsi yes yes no 175 0 NLMOHE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 178 0 NLNACN+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 181 0 NLNCGC+Arial,Italic TrueType WinAnsi yes yes no 198 0 NLMOHA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 201 0 NLMOHB+PalatinoLinotype CID TrueType Identity-H yes yes yes 204 0 NLMOHC+PalatinoLinotype TrueType WinAnsi yes yes no 210 0 NLMOHE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 213 0 NLNACN+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 216 0 NLMOHA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 236 0 NLMOHC+PalatinoLinotype TrueType WinAnsi yes yes no 239 0 NLMOHE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 242 0 NLNACN+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 245 0 NLMOHA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 267 0 NLMOHB+PalatinoLinotype CID TrueType Identity-H yes yes yes 270 0 NLMOHC+PalatinoLinotype TrueType WinAnsi yes yes no 276 0 NLMOHE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 279 0 NLNACN+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 282 0 NLMOHA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 303 0 NLMOHB+PalatinoLinotype CID TrueType Identity-H yes yes yes 306 0 NLMOHC+PalatinoLinotype TrueType WinAnsi yes yes no 312 0 NLMOHE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 315 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-02-02 02:35:36 CET RepresentationInformation: pmc_10095016.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-09-05 02:22:13 CEST Size: 4819351 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 631 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results and Discussion Destination: section.2 Children: Item: Title: Synthesis of AZM-SH and Anti-CAIX Action Destination: subsection.2.1 Item: Title: Docking Modelling and In Vitro Inhibition Studies Destination: subsection.2.2 Item: Title: NANO3-SH Characterization Destination: subsection.2.3 Item: Title: Loading and Release Assays. Proof of Concept: Enteric Coatings and Gastric Simulated Release Destination: subsection.2.4 Item: Title: Biofunctionalization Destination: subsection.2.5 Item: Title: Cytotoxicity, Antitumor Activity, Cellular Uptake, and Targetability Destination: subsection.2.6 Item: Title: Materials and Methods Destination: section.3 Children: Item: Title: Chemicals Destination: subsection.3.1 Item: Title: Instrumentation Destination: subsection.3.2 Item: Title: Synthesis and Characterization Destination: subsection.3.3 Children: Item: Title: N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl)-3-sulfanylpropanamide (AZM-SH) Synthesis Destination: subsubsection.3.3.1 Item: Title: Synthesis of NANO3-SH Destination: subsubsection.3.3.2 Item: Title: Modelling Studies and Molecular Docking Simulations Destination: subsection.3.4 Item: Title: CA In Vitro Inhibition Assay Destination: subsection.3.5 Item: Title: NANO3 Biofunctionalization with CTX-SH and AZM-SH Destination: subsection.3.6 Item: Title: Drug Loading and Release Assays Destination: subsection.3.7 Item: Title: Enteric Coatings and Simulated Digestive Track Release Destination: subsection.3.8 Item: Title: CA-IX and EGFR Expression in CRC Cell Lines Destination: subsection.3.9 Item: Title: Cytotoxicity and Cellular Uptake Destination: subsection.3.10 Item: Title: Conclusions Destination: section.4 Item: Title: References Destination: section.A. Info: Title: Development of New Targeted Nanotherapy Combined with Magneto-Fluorescent Nanoparticles against Colorectal Cancer Author: Gonçalo A. Marcelo, David Montpeyó, Joana Galhano, Ramón Martínez-Máñez, José Luis Capelo-Martínez, Julia Lorenzo, Carlos Lodeiro and Elisabete Oliveira Subject: The need for non-invasive therapies capable of conserving drug efficiency and stability while having specific targetability against colorectal cancer (CRC), has made nanoparticles preferable vehicles and principal building blocks for the development of complex and multi-action anti-tumoral approaches. For that purpose, we herein report the production of a combinatory anti-tumoral nanotherapy using the production of a new targeting towards CRC lines. To do so, Magneto-fluorescent NANO3 nanoparticles were used as nanocarriers for a combination of the drugs doxorubicin (DOX) and ofloxacin (OFLO). NANO3 nanoparticles’ surface was modified with two different targeting agents, a newly synthesized (anti-CA IX acetazolamide derivative (AZM-SH)) and a commercially available (anti-epidermal growth factor receptor (EGFR), Cetuximab). The cytotoxicity revealed that only DOX-containing nanosystems showed significant and even competitive cytotoxicity when compared to that of free DOX. Interestingly, surface modification with AZM-SH promoted an increased cellular uptake in the HCT116 cell line, surpassing even those functionalized with Cetuximab. The results show that the new target has high potential to be used as a nanotherapy agent for CRC cells, surpassing commercial targets. As a proof-of-concept, an oral administration form of NANO3 systems was successfully combined with Eudragit® enteric coating and studied under extreme conditions. 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Checksum: 0438d0661f70a17530425d3a5f2be124 Type: MD5 Checksum: 883dd7b779f3869f563db112f28df5488c725615 Type: SHA-1 Checksum: 986fa5cf1fd306ae54e6eb5e3dbcc9b2781b87175671feb87ce3ce22bdb34908 Type: SHA-256