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ACS Appl Mater Interfaces ; 9(26): 21697-21705, 2017 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-28590715


Aluminum-salt-based vaccine adjuvants are prevailingly used in FDA-approved vaccines for the prevention of infectious diseases for over eighty years. Despite their safe applications, the mechanisms regarding how the material characteristics affect the interactions at nano-bio interface and immunogenicity remain unclear. Recently, studies have indicated that the activation of NLRP3 inflammasome plays a critical role in inducing adjuvant effects that are controlled by the inherent shape and hydroxyl contents of aluminum oxyhydroxide (AlOOH) nanoparticles; however, the detailed relationship between surface properties and adjuvant effects for these materials remains unknown. Thus, we engineered AlOOH nanorods (ALNRs) with controlled surface functionalization and charge to assess their effects on the activation of NLRP3 inflammasome in vitro and the potentiation of immunogenicity in vivo. It is demonstrated that NH2-functionalized ALNRs exhibited higher levels of cellular uptake, lysosomal damage, oxidative stress, and NLRP3 inflammasome activation than pristine and SO3H-functionalized ALNRs in cells. This structure-activity relationship also correlates with the adjuvant activity of the material using ovalbumin (OVA) in a mouse vaccination model. This study demonstrates that surface functionalization of ALNRs is critical for rational design of aluminum-based adjuvants to boost antigen-specific immune responses for more effective and long-lasting vaccination.

Nanotubos , Adjuvantes Imunológicos , Alumínio , Animais , Inflamassomos , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ovalbumina
ACS Nano ; 10(8): 8054-66, 2016 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-27483033


Contrary to the notion that the use of fumed silica in consumer products can "generally (be) regarded as safe" (GRAS), the high surface reactivity of pyrogenic silica differs from other forms of synthetic amorphous silica (SAS), including the capacity to induce membrane damage and acute proinflammatory changes in the murine lung. In addition, the chain-like structure and reactive surface silanols also allow fumed silica to activate the NLRP3 inflammasome, leading to IL-1ß production. This pathway is known to be associated with subchronic inflammation and profibrogenic effects in the lung by α-quartz and carbon nanotubes. However, different from the latter materials, bolus dose instillation of 21 mg/kg fumed silica did not induce sustained IL-1ß production or subchronic pulmonary effects. In contrast, the NLRP3 inflammasome pathway was continuously activated by repetitive-dose administration of 3 × 7 mg/kg fumed silica, 1 week apart. We also found that while single-dose exposure failed to induce profibrotic effects in the lung, repetitive dosing can trigger increased collagen production, even at 3 × 3 mg/kg. The change between bolus and repetitive dosing was due to a change in lung clearance, with recurrent dosing leading to fumed silica biopersistence, sustained macrophage recruitment, and activation of the NLRP3 pathway. These subchronic proinflammatory effects disappeared when less surface-reactive titanium-doped fumed silica was used for recurrent administration. All considered, these data indicate that while fumed silica may be regarded as safe for some applications, we should reconsider the GRAS label during repetitive or chronic inhalation exposure conditions.

Inflamassomos , Pulmão/química , Nanotubos de Carbono , Dióxido de Silício/química , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Relação Estrutura-Atividade
J Nanosci Nanotechnol ; 16(3): 2390-3, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27455646


Therapeutic strategies to promote nerve cell growth and improve their functions or stimulate nerve fiber reconnection and ameliorate the loss of neuronal functions are in high demand. A disadvantage of current conventional methods, which includes injection of nerve growth factors (NGF) either systemically or in the affected area, is rapid clearance or degradation of NGF, thereby reducing the effective concentration of NGFs that can reach the damaged nerves to stimulate the healing process. To overcome this obstacle, a nanoparticle platform based on mesoporous silica nanoparticles (MSNs) was developed to not only prevent clearance and degradation of NGFs, but also deliver the NGF directly to nerve cells to promote nerve cell proliferation and neurite growth. We synthesized (NGF)-loaded MSN (MSN-NGF) with a diameter of 65 nm. MSN-NGF significantly promoted the differentiation of neuron-like PC12 cells and growth of neurites compared to NGF alone, as confirmed by MTS cell proliferation assay and optical microscopy analysis. This study shows that MSN-NGF could be an effective therapy to speed up nerve cell growth or recovery of function.

Nanopartículas , Fator de Crescimento Neural/farmacologia , Neurônios/efeitos dos fármacos , Dióxido de Silício/química , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fator de Crescimento Neural/química , Neurônios/citologia , Células PC12 , Ratos