title: Implantable controlled release devices for BMP-7 delivery and suppression of glioblastoma initiating cells.
abstract: Designing therapeutic devices capable of manipulating glioblastoma initiating cells (GICs) is critical to stop tumor recurrence and its associated mortality. Previous studies have indicated that bone morphogenetic protein-7 (BMP-7) acts as an endogenous suppressor of GICs, and thus, it could become a treatment for this cancer. In this work, we engineer an implantable microsphere system optimized for the controlled release of BMP-7 as a bioinspired therapeutic device against GICs. This microsphere delivery system is based on the formation of a heparin-BMP-7 nanocomplex, first coated with Tetronic(®) and further entrapped in a biodegradable polyester matrix. The obtained microspheres can efficiently encapsulate BMP-7, and release it in a controlled manner with minimum burst effect for over two months while maintaining protein bioactivity. Released BMP-7 showed a remarkable capacity to stop tumor formation in a GICs cell culture model, an effect that could be mediated by forced reprogramming of tumorigenic cells towards a non-tumorigenic astroglial lineage.
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Dept. Pharmacy and Pharmaceutical Technology and Health Research Institute of Santiago de Compostela (IDIS), Campus Vida, Universidad de Santiago de Compostela, Spain; Institute of Materials Science and Technology (IMRE), University of Havana, Cuba.
authors.forename: Elaine
authors.initials: E
authors.lastname: Reguera-Nuñez
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Dept. Pharmacy and Pharmaceutical Technology and Health Research Institute of Santiago de Compostela (IDIS), Campus Vida, Universidad de Santiago de Compostela, Spain.
authors.forename: Carlota
authors.initials: C
authors.lastname: Roca
authors.affiliation: Institute of Materials Science and Technology (IMRE), University of Havana, Cuba.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Hardy
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Dept. Pharmacy and Pharmaceutical Technology and Health Research Institute of Santiago de Compostela (IDIS), Campus Vida, Universidad de Santiago de Compostela, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: de la Fuente
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Dept. Pharmacy and Pharmaceutical Technology and Health Research Institute of Santiago de Compostela (IDIS), Campus Vida, Universidad de Santiago de Compostela, Spain.
authors.forename: Noemi
authors.initials: N
authors.lastname: Csaba
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Dept. Pharmacy and Pharmaceutical Technology and Health Research Institute of Santiago de Compostela (IDIS), Campus Vida, Universidad de Santiago de Compostela, Spain. Electronic address: marcos.garcia@usc.es.
authors.forename: Marcos
authors.initials: M
authors.lastname: Garcia-Fuentes
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology / Q000627:therapeutic use*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008863:Microspheres; D053758:Nanoparticles / Q000648:ultrastructure; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011108:Polymers / Q000737:chemistry; D019736:Prostheses and Implants; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D055419:Bone Morphogenetic Protein 7; D003692:Delayed-Action Preparations; D011108:Polymers; D001973:Bromodeoxyuridine
keywords: Bone morphogenetic protein; Cancer initiating cells; Controlled release; Glioblastoma; Microspheres; PLGA