title: Hybrid Collagenase Nanocapsules for Enhanced Nanocarrier Penetration in Tumoral Tissues.
abstract: Poor penetration of drug delivery nanocarriers within dense extracellular matrices constitutes one of the main liabilities of current nanomedicines. The conjugation of proteolytic enzymes on the nanoparticle surface constitutes an attractive alternative. However, the scarce resistance of these enzymes against the action of proteases or other aggressive agents present in the bloodstream strongly limits their application. Herein, a novel nanodevice able to transport proteolytic enzymes coated with an engineered pH-responsive polymeric is presented. This degradable coat protects the housed enzymes against proteolytic attack at the same time that it triggers their release under mild acidic conditions, usually present in many tumoral tissues. These enzyme nanocapsules have been attached on the surface of mesoporous silica nanoparticles, as nanocarrier model, showing a significatively higher penetration of the nanoparticles within 3D collagen matrices which housed human osteosarcoma cells (HOS). This strategy can improve the therapeutic efficacy of the current nanomedicines, allowing a more homogeneous and deeper distribution of the therapeutic nanosystems in cancerous tissues.
authors.affiliation: Departamento Química Inorgánica y Bioinorgánica, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12 , Plaza Ramón y Cajal s/n, Madrid 28040, Spain.|Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) , Avenida Monforte de Lemos, 3-5, Madrid 28029, Spain.
authors.forename: María Rocío
authors.initials: MR
authors.lastname: Villegas
authors.affiliation: Departamento Química Inorgánica y Bioinorgánica, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12 , Plaza Ramón y Cajal s/n, Madrid 28040, Spain.|Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) , Avenida Monforte de Lemos, 3-5, Madrid 28029, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Baeza
authors.affiliation: Departamento Química Inorgánica y Bioinorgánica, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12 , Plaza Ramón y Cajal s/n, Madrid 28040, Spain.|Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) , Avenida Monforte de Lemos, 3-5, Madrid 28029, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Vallet-Regí
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003094:Collagen / Q000737:chemistry; D017364:Collagenases / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004798:Enzymes / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053769:Nanocapsules / Q000737:chemistry*; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D011108:Polymers / Q000737:chemistry; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D004798:Enzymes; D053769:Nanocapsules; D011108:Polymers; D012822:Silicon Dioxide; D003094:Collagen; D007770:L-Lactate Dehydrogenase; D017364:Collagenases
keywords: collagenase nanocapsules; mesoporous silica nanodevices and hybrid nanocarriers; nanomedicine; tumoral tissue penetration