title: Spherical polymeric nanoconstructs for combined chemotherapeutic and anti-inflammatory therapies.
abstract: Nanoparticles can simultaneously deliver multiple agents to cancerous lesions enabling de facto combination therapies. Here, spherical polymeric nanoconstructs (SPNs) are loaded with anti-cancer - docetaxel (DTXL) - and anti-inflammatory - diclofenac (DICL) - molecules. In vitro, combination SPNs kill U87-MG cells twice as efficiently as DTXL SPNs, achieving a IC50of 90.5nM at 72h. Isobologram analysis confirms a significant synergy (CI=0.56) between DTXL and DICL. In mice bearing non-orthotopic glioblastoma multiforme tumors, combination SPNs demonstrate higher inhibition in disease progression. At 70days post treatment, the survival rate of mice treated with combination SPNs is of about 70%, against a 40% for DTXL SPNs and 0% for free DTXL. Combination SPNs dramatically inhibit COX-2 expression, modulating the local inflammatory status, and increase Caspase-3 expression, which is directly related to cell death. These results suggest that the combination of anti-cancer and anti-inflammatory molecules constitutes a potent strategy for inhibiting tumor growth.
authors.affiliation: Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Aeju
authors.initials: A
authors.lastname: Lee
authors.affiliation: Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Mascolo
authors.affiliation: Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Francardi
authors.affiliation: Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Piccardi
authors.affiliation: Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Bandiera
authors.affiliation: Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy. Electronic address: Paolo.Decuzzi@iit.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Decuzzi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D053148:Caspase 3; D016923:Cell Death; D005909:Glioblastoma / Q000188:drug therapy*; D051379:Mice; D053758:Nanoparticles; D011108:Polymers
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D011108:Polymers; D053148:Caspase 3
keywords: Cancer inflammation; Combinatorial therapy; Nanoparticles; Tumor microenvironment