3526913c63a56d803a0bae0d4ac2ce66 pmc_9003391.pdf 95bd97f27c5ed651df71aa3e0efbd53a855d2c13 pmc_9003391.pdf dfd0112e740d4fdc2c19099e10d882bf00dd08d7d2bd33862e99772bf2964544 pmc_9003391.pdf Title: Intranasal Administration of Catechol-Based Pt(IV) Coordination Polymer Nanoparticles for Glioblastoma Therapy Subject: Cisplatin has been described as a potent anticancer agent for decades. However, in the case of glioblastomas, it is only considered a rescue treatment applied after the failure of second-line treatments. Herein, based on the versatility offered by coordination chemistry, we engineered nanoparticles by reaction of a platinum (IV) prodrug and iron metal ions showing in vitro dual pH- and redox-sensitivity, controlled release and comparable cytotoxicity to cisplatin against HeLa and GL261 cells. In vivo intranasal administration in orthotopic preclinical GL261 glioblastoma tumor-bearing mice demonstrated increased accumulation of platinum in tumors, leading in some cases to complete cure and prolonged survival of the tested cohort. This was corroborated by a magnetic resonance imaging follow-up, thus opening new opportunities for intranasal glioblastoma therapies while minimizing side effects. The findings derived from this research showed the potentiality of this approach as a novel therapy for glioblastoma treatment. Keywords: nanoscale coordination polymers; platinum; catechol; intranasal administration; glioblastoma; preclinical studies; GL261 GB; magnetic resonance imaging Author: Xiaoman Mao, Pilar Calero-Pérez, David Montpeyó, Jordi Bruna, Victor J. Yuste, Ana Paula Candiota, Julia Lorenzo, Fernando Novio and Daniel Ruiz-Molina Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Apr 6 12:06:03 2022 CEST ModDate: Wed Apr 6 12:36:47 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3580081 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YSAOHE+VnURWPalladioL Type 1 Custom yes yes no 10 0 YJUZRI+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 ZKYUIV+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 JLOCIH+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 HJOMHV+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 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edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Estimation of ROS Formation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Animal Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: GL261 GB Preclinical Model Generation and Animal Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Children: Item: Title: Tumor Generation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Tumor-Bearing Mice Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Tissue Preservation Procedures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: In Vivo MRI Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Tolerability Assays Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: 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edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: Cell Internalization and DNA-Bound Pt Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: ROS Production in GL261 cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: In Vivo Tolerability and Biodistribution via Intranasal Administration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: In Vivo Anticancer Efficacy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Children: Item: Title: Advantages of Pt(IV) Prodrug Nanoformulation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Item: Title: In Vivo Efficacy Is Not Directly Related to the Paradigm “More Is Better”: Words of Caution Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Info: Title: Intranasal Administration of Catechol-Based Pt(IV) Coordination Polymer Nanoparticles for Glioblastoma Therapy Author: Xiaoman Mao, Pilar Calero-Pérez, David Montpeyó, Jordi Bruna, Victor J. Yuste, Ana Paula Candiota, Julia Lorenzo, Fernando Novio and Daniel Ruiz-Molina Subject: Cisplatin has been described as a potent anticancer agent for decades. However, in the case of glioblastomas, it is only considered a rescue treatment applied after the failure of second-line treatments. Herein, based on the versatility offered by coordination chemistry, we engineered nanoparticles by reaction of a platinum (IV) prodrug and iron metal ions showing in vitro dual pH- and redox-sensitivity, controlled release and comparable cytotoxicity to cisplatin against HeLa and GL261 cells. In vivo intranasal administration in orthotopic preclinical GL261 glioblastoma tumor-bearing mice demonstrated increased accumulation of platinum in tumors, leading in some cases to complete cure and prolonged survival of the tested cohort. This was corroborated by a magnetic resonance imaging follow-up, thus opening new opportunities for intranasal glioblastoma therapies while minimizing side effects. The findings derived from this research showed the potentiality of this approach as a novel therapy for glioblastoma treatment. 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