title: Functionalized mesoporous silica nanoparticles: a possible strategy to target cancer cells reducing peripheral nervous system uptake.
abstract: Mesoporous silica materials (MSM) have been proposed as promising tools for cell specific drug delivery or fluorescent cell tracking. In cancer therapy there is an urgent need to develop a cancer cell specific drug carrier able to limit the non-specific uptake of the drug by normal cells thereby reducing serious side effects. Chemotherapy induced peripheral neurotoxicity (CIPN) is one of the most clinically relevant side effects linked to the use of several antineoplastic drugs. In this study we showed that the uptake of MSM (synthesized using a PEG surfactant-based interfacial synthesis procedure), functionalised with folic acid (MSM-FOL) after 1, 6 and 24 hours is very limited in neuronal-like cellular systems such as differentiated SH-SY5Y human neuroblastoma cells and rat embryonic dorsal root ganglia sensory neurons. By contrast, the nanoparticles are highly internalized in A549 and IGROV-1 cancer cells. The 6 hour-treatment of A549 and IGROV-1 cells with nanoparticles loaded with the antineoplastic drug cisplatin (CP) induced significant cytotoxicity with respect to CP alone. These results were observed treating IGROV-1 cells with 25 and 50 μg/ml nanoparticles doses (corresponding respectively to CP 6.25 and 12.5 μM) and treating A549 with 50 μg/ml.Our results demonstrated a selective uptake of functionalized MSM suggesting them as promising tools for targeted antineoplastic therapy. Further studies will be necessary in order to confirm if this approach may be useful in reducing neurotocity of anticancer drugs.
authors.affiliation: Dipartimento di Chirurgia e Medicina Interdisciplinare, Università di Milano Bicocca, Monza, Italy. cecilia.ceresa1@unimib.it
authors.forename: C
authors.initials: C
authors.lastname: Ceresa
authors.forename: G
authors.initials: G
authors.lastname: Nicolini
authors.forename: R
authors.initials: R
authors.lastname: Rigolio
authors.forename: M
authors.initials: M
authors.lastname: Bossi
authors.forename: L
authors.initials: L
authors.lastname: Pasqua
authors.forename: G
authors.initials: G
authors.lastname: Cavaletti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D058975:Folate Receptor 1 / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D058975:Folate Receptor 1; D012822:Silicon Dioxide; D016650:Fluorescein-5-isothiocyanate; D002945:Cisplatin