title: Tailoring Particle Size of Mesoporous Silica Nanosystem To Antagonize Glioblastoma and Overcome Blood-Brain Barrier.
abstract: The blood-brain barrier (BBB) is the main bottleneck to prevent some macromolecular substance entering the cerebral circulation, resulting the failure of chemotherapy in the treatment of glioma. Cancer nanotechnology displays potent applications in glioma therapy owing to their penetration across BBB and accumulation into the tumor core. In this study, we have tailored the particle size of mesoporous silica nanoparticles (MSNs) through controlling the hydrolysis rate and polycondensation degree of reactants, and optimized the nanosystem that could effectively penetrate BBB and target the tumor tissue to achieve enhanced antiglioma efficacy. The nanoparticle was conjugated with cRGD peptide to enhance its cancer targeting effect, and then used to load antineoplastic doxorubicin. Therefore, the functionalized nanosystem (DOX@MSNs) selectively recognizes and binds to the U87 cells with higher expression level of ανβ3 integrin, sequentially enhancing the cellular uptake and inhibition to glioma cells, especially the particle size at 40 nm. This particle could rapidly enter cancer cells and was difficult to excrete outside the cells, thus leading to high drug accumulation. Furthermore, DOX@MSNs exhibited much higher selectivity and anticancer activity than free DOX and induced the glioma cells apoptosis through triggering ROS overproduction. Interestingly, DOX@MSNs at about 40 nm exhibited stronger permeability across the BBB, and could disrupt the VM-capability of glioma cells by regulating the expression of E-cadherin, FAK, and MMP-2, thus achieving satisfactory antiglioblastoma efficacy and avoiding the unwanted toxic side effects to normal brain tissue. Taken together, these results suggest that tailoring the particle size of MSNs nanosystem could be an effective strategy to antagonize glioblastoma and overcome BBB.
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Mo
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D016062:Porosity; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: BBB; apoptosis; glioblastoma; mesoporous silica nanosystem; particle size