Sustained release of PKR inhibitor C16 from mesoporous silica nanoparticles significantly enhances mRNA translation and anti-tumor vaccination

2021 ◽  
Vol 163 ◽  
pp. 179-187
Author(s):  
Wei Zhang ◽  
Yi Liu ◽  
Jas Min Chin ◽  
Kyle K.L. Phua
Keyword(s):  
Mesoporous Silica ◽  
Sustained Release ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Mrna Translation ◽  
Tumor Vaccination

scholarly journals PEI-PEG-Coated Mesoporous Silica Nanoparticles Enhance the Antitumor Activity of Tanshinone IIA and Serve as a Gene Transfer Vector

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yinxing Zhu ◽  
Miao Yue ◽  
Ting Guo ◽  
Fang Li ◽  
Zhifeng Li ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Antitumor Activity ◽  
Mesoporous Silica ◽  
Sustained Release ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Carrier ◽  
Tanshinone Iia

Tanshinone IIA (TanIIA) and gene therapy both hold promising potentials in hepatocellular carcinoma (HCC) treatment. However, low solubility and poor bioavailability of TanIIA limit its clinical application. Similarly, gene therapy with GPC3-shRNA, a type of short hairpin RNAs (shRNAs) capable of silencing the glypican-3 (GPC3) expression, is seriously limited due to its susceptibility to nuclease degradation and high off-target effects. In the present study, polyethyleneimine (PEI)-polyethylene glycol (PEG)-coated mesoporous silica nanoparticles (MSN-PEG) were used as a drug carrier. By encapsulating TanIIA into MSN-PEG, we synthesized MSN-TanIIA-PEG nanoparticles and observed the involved characteristics. This was followed by exploration of antitumor activity on the HepG2 cell lines in vitro. Meanwhile, in order to construct GPC3-shRNA plasmids, a shRNA sequence targeting GPC3 was synthesized and cloned into the pSLenti-U6 vector. Accordingly, the performance of MSN-PEG as a gene transfer carrier for GPC3-shRNA gene therapy of HCC in vitro was evaluated, including transfection efficiency and DNA binding biological characteristics. The results indicated successful encapsulation of TanIIA in MSN-PEG, which had satisfactory efficacy, favorable dispersity, suitable particle size, and sustained release effect. The in vitro anti-HCC effects of nano-TanIIA were greatly improved, which outperformed free-TanIIA in terms of proliferation and invasion inhibition, as well as apoptosis induction of HCC cells. As expected, MSN-PEG possessed excellent gene delivery capacity with good binding, release, and protection from RNase digestion. Using MSN-PEG as a gene carrier, the plasmids were successfully transfected into HepG2 cells, and both the mRNA and protein expressions of GPC3 were significantly downregulated. It was thus concluded that a sustained release TanIIA delivery system for HCC treatment was synthesized and that MSN-PEG could also serve as a gene transfer carrier for gene therapy. More interestingly, MSN-PEG may be a potential delivery platform that combines TanIIA and GPC3-shRNA together to enhance their synergistic effect.

scholarly journals In Vivo Sustained Release of Peptide Vaccine Mediated by Dendritic Mesoporous Silica Nanocarriers

2021 ◽  
Vol 12 ◽  
Author(s):  
Weiteng An ◽  
Sira Defaus ◽  
David Andreu ◽  
Pilar Rivera-Gil
Keyword(s):  
Mesoporous Silica ◽  
Sustained Release ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Peptide Vaccine ◽  
Vaccine Delivery ◽  
Dependent Manner ◽  
Mouth Disease Virus

Mesoporous silica nanoparticles have drawn increasing attention as promising candidates in vaccine delivery. Previous studies evaluating silica-based vaccine delivery systems concentrated largely on macromolecular antigens, such as inactivated whole viruses. In this study, we synthesized dendritic mesoporous silica nanoparticles (DMSNs), and we evaluated their effectiveness as delivery platforms for peptide-based subunit vaccines. We encapsulated and tested in vivo an earlier reported foot-and-mouth disease virus (FMDV) peptide vaccine (B2T). The B2T@DMSNs formulation contained the peptide vaccine and the DMSNs without further need of other compounds neither adjuvants nor emulsions. We measured in vitro a sustained release up to 930 h. B2T@DMSNs-57 and B2T@DMSNs-156 released 23.7% (135 µg) and 22.8% (132 µg) of the total B2T. The formation of a corona of serum proteins around the DMSNs increased the B2T release up to 61% (348 µg/mg) and 80% (464 µg/mg) for B2T@DMSNs-57 and B2T@DMSNs-156. In vitro results point out to a longer sustained release, assisted by the formation of a protein corona around DMSNs, compared to the reference formulation (i.e., B2T emulsified in Montanide). We further confirmed in vivo immunogenicity of B2T@DMSNs in a particle size-dependent manner. Since B2T@DMSNs elicited specific immune responses in mice with high IgG production like the reference B2T@Montanide™, self-adjuvant properties of the DMSNs could be ascribed. Our results display DMSNs as efficacious nanocarriers for peptide-based vaccine administration.

Gelatin-functionalized mesoporous silica nanoparticles with sustained release properties for intracameral pharmacotherapy of glaucoma

2017 ◽  
Vol 5 (34) ◽  
pp. 7008-7013 ◽  
Author(s):  
Yu-Te Liao ◽  
Chih-Hung Lee ◽  
Si-Tan Chen ◽  
Jui-Yang Lai ◽  
Kevin C.-W. Wu
Keyword(s):  
Intraocular Pressure ◽  
Mesoporous Silica ◽  
Sustained Release ◽  
Anterior Chamber ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Functionalized Mesoporous Silica

Herein, pilocarpine-loaded gelatin-covered mesoporous silica nanoparticles (denoted as p/GM) were intracamerally administrated into the anterior chamber for the reduction of intraocular pressure (IOP).

Hybrid biomaterial based on porous silica nanoparticles and Pluronic F-127 for sustained release of sildenafil: in vivo study on prostate cancer

RSC Advances ◽  
2015 ◽  
Vol 5 (99) ◽  
pp. 81348-81355 ◽  
Author(s):  
C. P. Silveira ◽  
L. M. Apolinário ◽  
W. J. Fávaro ◽  
A. J. Paula ◽  
N. Durán
Keyword(s):  
Prostate Cancer ◽  
Mesoporous Silica ◽  
Sustained Release ◽  
Silica Nanoparticles ◽  
High Efficiency ◽  
Mesoporous Silica Nanoparticles ◽  
Porous Silica ◽  
In Vivo Study ◽  
Hydrogel System

We describe here a drug depot hydrogel system comprising sildenafil (Viagra®) incorporated in mesoporous silica nanoparticles (60 nm) and conjugated with a thermosensitive poloxamer, which presents a high efficiency against prostate cancer.

Sign in / Sign up

Export Citation Format

Share Document