Mesoporous Silica Nanoparticles For Delivery Research Articles

Preparation of melamine-functionalized mesoporous silica nanoparticles for delivery of anticancer drugs

The surface-grafted mesoporous silica nanoparticles attract interest in drug delivery, owing to their high drug loading and controlled release potential to the target sites. In this paper, we propose the synthesis of mesoporous silica nanoparticles and their surface grafting using melamine groups for pH-responsive release of anticancer drugs. A model anticancer drug, 5-fluorouracil (5-Fu) was used to encapsulate into the melamine-grafted mesoporous silica nanoparticles (M−MS/5-Fu NPs) using the solvent immersion method. pH and temperature-responsive release behavior of the M−MS/5-Fu NPs were verified at different pH (pH 7.4, 6.5, and 4.0). Further, the in vitro cytotoxicity of the prepared samples was also evaluated on the MCF-7 cell line.

A pH-responsive chiral mesoporous silica nanoparticles for delivery of doxorubicin in tumor-targeted therapy

The purpose of this study was to develop a nano-drug delivery system with intelligent stimuli-responsive drug delivery in tumor microenvironment (TME). Based on chiral mesoporous silica nanoparticles (CMSN) with a chiral recognition function in our previous research, a pH-responsive CMSN (CS-CMSN) was successfully prepared by chemical modification of chitosan (CS), and the related physicochemical properties, drug release performance, potential anti-tumor effect, and biological safety were studied. The results showed that the CS-CMSN were successfully modified by CS. Moreover, CS-CMSN displayed superior encapsulation ability for doxorubicin (DOX) and exhibited controllable pH-responsive drug release properties. In particular, in a physiological environment (pH 7.4/6.5), CS shielded the nanopores, prevented DOX release, and minimized side effects on normal cells. Once the CS-CMSN was exposed to the TME (pH 5.0), the pH-sensitive moiety of CS was cleaved in an acidic environment, along with the rapid release of DOX. In vitro cell experiments further proved that DOX@CS-CMSN was more strongly taken up by 4T1 cells and could enhance the toxicity to 4T1 tumor cells as well as promote cell apoptosis. More importantly, CS-CMSN were shown to have good biosafety in vitro and in vivo. Overall, the delivery of DOX by CS-CMSN nanocarriers is a promising strategy for tumor-targeted therapy.

PH-responsive Glucosamine Anchored Polydopamine Coated Mesoporous Silica Nanoparticles for delivery of Anderson-type Polyoxomolybdate in Breast Cancer

Aim This study aimed to develop novel pH-sensitive Glucosamine (Glu) targeted Polydopamine (PDA) coated mesoporous silica (SBA-15) nanoparticles (NPs) for selective delivery of anticancer Anderson-type manganese polyoxomolybdate (POMo) to breast cancer. Methods The POMo@SBA-PDA-Glu NPs were prepared via direct hydrothermal synthesis of SBA, POMo loading, in situ PDA post functionalization, and Glu anchoring; the chemical structures were fully studied by different characterization methods. The anticancer activity was studied by MTT method and Annexin V-FITC apoptosis detection kit. Results The optimized NPs had a hydrodynamic size (HS) of 195 nm, a zeta potential (ZP) of -18.9 mV, a loading content percent (LC%) of 45%, and a pH-responsive release profile. The targeted NPs showed increased anticancer activity against breast cancer cell lines compared to the free POMo with the highest cellular uptake and apoptosis level in the MDA-MB-231 cells. Conclusions POMo@SBA-PDA-Glu NPs could be a promising anticancer candidate for further studies.

Smart pH responsive system based on hybrid mesoporous silica nanoparticles for delivery of fungicide to control Fusarium crown and root rot in tomato

Mesoporous silica nanoparticles (MSNs) can promote the solubility and absorption of pesticides by plants and are widely used as a delivery system to improve the efficacy of pesticide applications. In this study, MSNs with 20 nm particle size were produced. Additionally, a water-soluble chitosan (CS) derivative, here called N-(2-Hydroxyl) propyl-3- tri-methyl-ammonium CS chloride (HTCC) was produced and used to cap the outer surface of the MSNs preloaded with the pesticide fludioxonil (Flu). The HTCC coating layers resulted in a pesticide loading efficiency of 84% on the MSNs in comparison to a loading efficiency of 20% of uncoated particles. A comparative in vitro analysis indicated that Flu@MSNs20nm-HTCC loaded with a 0.05 mg/L dose of fungicide had significant higher fungicidal activity than the same fungicide at 1 mg/L dose against F. oxysporum f. sp. radicis-lycopersici (FORL). Moreover, after an initial burst, MSNs20nm-HTCC kept releasing Flu for 21 d, compared to an activity of 7 d associated with the direct release of Flu. Greenhouse data showed that 0.1 mg/L Flu applied through MSNs20nm-HTCC is sufficient to reduce Fusarium crown and root rot disease severity to a value of less than 6% in tomato plants, without any noticeable phytotoxicity after 70 d. In comparison, 1.56 mL/L of the fungicide are required to reach a 27% disease severity level. Thus, we suggest that HTCC-decorated MSNs20nm has a great potential as a nanodelivery systems for agrochemical applications. We also suggest that this work contributes to the notion that agro-nanotechnology is a powerful, environmentally-safe and cost-effective approach for a sustainable and long term protection of plants from disease.

Biodegradable nanocarriers based on chitosan-modified mesoporous silica nanoparticles for delivery of methotrexate for application in breast cancer treatment

Nanocarriers have demonstrated great promise in the delivery of hydrophobic drugs particularly to tumor spaces by enhanced permeability and retention (EPR) effects. Mesoporous silica nanoparticles (MSNs) are the attractive nanocarrier system to reduce the drug's toxic side effects, enable controlled drug release, prevent drug degradation and provide a biocompatible and biodegradable high surface area carrier. Surface-modified MSNs have been applied to increase drug loading and efficiency. In this study, functionalized MSNs loaded with methotrexate (MTX) were designed for use as a cytotoxic agent. The MSNs were first modified with 3-triethoxysilylpropylamine (APTES) and then with chitosan through covalent coupling mediated by glutaraldehyde. The physicochemical properties of the nanoparticles were optimized for each step. The loading percentage (12.2%) and release profile of MTX as an anti-breast cancer drug, loaded at amine-modified MSNs, were measured via high performance liquid chromatography (HPLC). Moreover, the uptake profiles of fluorescein isothiocyanate (FITC)-labeled MSN-APTES-chitosan with or without MTX were monitored on MCF7 cancer cells via confocal microscopy. Following exposure of nanoparticles to body fluids, they were surrounded by specific proteins that may affect their cellular uptake. Hence, the adsorption profiles of protein corona on the surface of MSN, amine-modified MSN and MTX-loaded MSN-APTES-chitosan were analyzed. The cytotoxic potential for killing breast cancer cells was also studied. The MTX loaded MSN-APTES-chitosan showed a positive effect at a low dose (0.5 μM MTX). In this study, we introduce a new method to synthesize biodegradable MSNs with small and uniform particle size, achieve high MTX loading via covalent amine and chitosan-functionalization, monitor the cellular uptake and demonstrate the potential to decrease the viability of breast cancer cells at low dose.

Intrinsic Biotaxi Solution Based on Blood Cell Membrane Cloaking Enables Fullerenol Thrombolysis In Vivo.

We report the construction of blood cell membrane cloaked mesoporous silica nanoparticles for delivery of nanoparticles [fullerenols (Fols)] with fibrinolysis activity which endows the active Fol with successful thrombolysis effect in vivo. In vitro, Fols present excellent fibrinolysis activity, and the Fol with the best fibrinolysis activity is screened based on the correlation between Fols' structure and their fibrinolysis activity. However, the thrombolytic effect in vivo is not satisfactory. To rectify the unsatisfactory situation and avoid the exogenous stimuli, a natural blood cell membrane cloaking strategy with loading the active Fol is chosen to explore as a novel thrombolysis drug. After cloaking, the therapeutic platform prolongs blood circulation time and enhances the targeting effect. Interestingly, compared with platelet membrane cloaking, red blood cell (RBC) membrane cloaking demonstrates stronger affinity with fibrin and more enrichment at the thrombus site. The Fol with RBC cloaking shows quick and efficient thrombolysis efficacy in vivo with less bleeding risk, more excellent blood compatibility, and better biosafety when compared with the clinical drug urokinase (UK). These findings not only validate the blood cell membrane cloaking strategy as an effective platform for Fol delivery on thrombolysis treatment, but also hold a great promising solution for other active nanoparticle deliveries in vivo.

Selective Photokilling of Human Pancreatic Cancer Cells Using Cetuximab-Targeted Mesoporous Silica Nanoparticles for Delivery of Zinc Phthalocyanine.

Background: Photodynamic therapy (PDT) is a non-invasive and innovative cancer therapy based on the photodynamic effect. In this study, we sought to determine the singlet oxygen production, intracellular uptake, and in vitro photodynamic therapy potential of Cetixumab-targeted, zinc(II) 2,3,9,10,16,17,23,24-octa(tert-butylphenoxy))phthalocyaninato(2-)-N29,N30,N31,N32 (ZnPcOBP)-loaded mesoporous silica nanoparticles against pancreatic cancer cells. Results: The quantum yield (ΦΔ) value of ZnPcOBP was found to be 0.60 in toluene. In vitro cellular studies were performed to determine the dark- and phototoxicity of samples with various concentrations of ZnPcOBP by using pancreatic cells (AsPC-1, PANC-1 and MIA PaCa-2) and 20, 30, and 40 J/cm2 light fluences. No dark toxicity was observed for any sample in any cell line. ZnPcOBP alone showed a modest photodynamic activity. However, when incorporated in silica nanoparticles, it showed a relatively high phototoxic effect, which was further enhanced by Cetuximab, a monoclonal antibody that targets the Epidermal Growth Factor Receptor (EGFR). The cell-line dependent photokilling observed correlates well with EGFR expression levels in these cells. Conclusions: Imidazole-capped Cetuximab-targeted mesoporous silica nanoparticles are excellent vehicles for the selective delivery of ZnPcOBP to pancreatic cancer cells expressing the EGFR receptor. The novel nanosystem appears to be a suitable agent for photodynamic therapy of pancreatic tumors.

Mesoporous materials used in medicine and environmental applications.

Mesoporous materials synthesized in the presence of templates, are commonly used for environment and medical applications. Due to the properties it holds, mesoporous silica nanoparticles is an excellent material for use in medical field, biomaterials, active principles delivery systems, enzyme immobilization and imaging. Their structure allows embedding large and small molecules, DNA adsorption and genetic transfer. Using mesoporous silica nanoparticles for delivery of bioactive molecules can protect them against degradation under physiological conditions, allow controlled drugs release and minimize side effects on healthy tissues. Cellular tests performed on mesoporous silica nanoparticles demonstrate that MSN's cytotoxicity is dependent on the size and concentration and suggests the use of larger size nanoparticles is optimal for medical applications. Mesoporous materials possess high biological compatibility, are non-toxic and can be easily modified by functionalizing the surface or inside the pores by grafting or co-condensation method. The structure, composition and pores size of this material can be optimized during synthesis by varying the stoichiometric reactants, reaction conditions, nature of the template's molecules or by functionalization method.