title: SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery.
abstract: In addition to surgery, local tumor control in pediatric oncology requires new treatments as an alternative to radiotherapy. SN-38 is an anticancer drug with proved activity against several pediatric solid tumors including neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. Taking advantage of the extremely low aqueous solubility of SN-38, we have developed a novel drug delivery system (DDS) consisting of matrices made of poly(lactic acid) electrospun polymer nanofibers loaded with SN-38 microcrystals for local release in difficult-to-treat pediatric solid tumors. To model the clinical scenario, we conducted extensive preclinical experiments to characterize the biodistribution of the released SN-38 using microdialysis sampling in vivo. We observed that the drug achieves high concentrations in the virtual space of the surgical bed and penetrates a maximum distance of 2 mm within the tumor bulk. Subsequently, we developed a model of subtotal tumor resection in clinically relevant pediatric patient-derived xenografts and used such models to provide evidence of the activity of the SN-38 DDS to inhibit tumor regrowth. We propose that this novel DDS could represent a potential future strategy to avoid harmful radiation therapy as a primary tumor control together with surgery.
authors.affiliation: Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Monterrubio
authors.affiliation: Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain.
authors.forename: Guillem
authors.initials: G
authors.lastname: Pascual-Pasto
authors.affiliation: Institut de Investigació Tèxtil i Cooperació Industrial de Terrassa (INTEXTER), Universitat Politecnica de Catalunya, Colom 15, Terrassa, 08222, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Cano
authors.affiliation: Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Vila-Ubach
authors.affiliation: Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain; Department of Pediatric Surgery, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Manzanares
authors.affiliation: CONICET-Clinical Pharmacokinetics Unit, Hospital de Pediatrίa JP Garrahan, Combate de los Pozos 1881, 1245, Buenos Aires, Argentina.
authors.forename: Paula
authors.initials: P
authors.lastname: Schaiquevich
authors.affiliation: Institut de Investigació Tèxtil i Cooperació Industrial de Terrassa (INTEXTER), Universitat Politecnica de Catalunya, Colom 15, Terrassa, 08222, Barcelona, Spain; Cebiotex Biomedical Nanofibers, Parc Cientific de Barcelona, Baldiri i Reixac 4, 08028, Barcelona, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Tornero
authors.affiliation: Department of Materials Science and Engineering, Technion-Israel Institute of Technology, Technion City, Haifa, Israel; Russell Berrie Nanotechnology Institute (RBNI), Technion-Israel Institute of Technology, Technion City, Haifa, Israel.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosnik
authors.affiliation: Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Mora
authors.affiliation: Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain. Electronic address: amontero@fsjd.org.
authors.forename: Angel M
authors.initials: AM
authors.lastname: Carcaboso
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002675:Child, Preschool; D004058:Diffusion; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery*; D010316:Particle Size; D011182:Postoperative Care / Q000379:methods; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053769:Nanocapsules; D000077146:Irinotecan; D002166:Camptothecin
keywords: Local chemotherapy delivery; Microdialysis; Pediatric solid tumor; Pharmacokinetics; Poly(lactic acid) electrospun nanofibers; SN-38