Mesoporous Silica Nanocarriers Research Articles

Polydopamine-coated matchstick-like mesoporous silica carriers for improving foliar retention and responsive pesticide release

Intelligent responsive pesticide delivery systems have gained extensive interest in enhancing utilization efficiency of pesticides and relieving environmental hazards. Herein, we developed a novel matchstick-like mesoporous silica (mSiO2) nanocarriers for pesticide delivery. The asymmetric matchstick-like mSiO2 carriers were composed by a spherical dendritic silica (SiO2) head (300 nm) and a rod-shaped tail (90 nm in length). This asymmetric structure would improve foliar retention by increasing contact area and forming topological effect between the carriers and the leaves surface. The prepared mSiO2 carriers possessed a high loading content for the insecticide dinotefuran (DNF) (23.7 %). Subsequently, polydopamine (PDA) was utilized to seal the DNF-loaded mSiO2 (DNF@mSiO2@PDA). The foliar affinity and adhesion properties of the mSiO2@PDA were enhanced due to the introduction of the hydrophilic PDA layer. The DNF@mSiO2@PDA exhibited pH-responsive release performance and the anti-UV property of loaded DNF was improved by about 10 times. Additionally, the DNF@mSiO2@PDA also exhibited high insecticidal activity due to the improving foliar wetting and affinity. Therefore, this work provides a promising strategy to increase pesticide retention on leaves and reduce pesticide chemical usage.

Evaluation of the Ocular Safety of Hollow Mesoporous Organosilica Nanoparticles with Different Tetrasulfur Bond Content.

Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers. In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections. In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H2S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities. The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.

Carriers for hydrophobic drug molecules: lipid-coated hollow mesoporous silica particles, and the influence of shape and size on encapsulation efficiency.

Hydrophobic drugs, while designed to interact with specific receptors or enzymes located in lipid-rich cell membranes, often face challenges of limited bioavailability and insufficient circulation time due to their insolubility in aqueous environments. One plausible pathway to increase their blood circulation time is to load these drugs into biocompatible and hydrophilic carriers to enhance their uptake. In this study, mesoporous silica (mSiO2) nanocarriers of various morphologies (including cubes, capsules, and spheres) were synthesized. These nanocarriers were then surface-functionalized with alkyl chain hydrocarbons, specifically octadecyl-trimethoxysilane, (OCH3)3Si(CH2)17CH3, to render them hydrophobic. The resulting nanocarriers (((OCH3)3Si(CH2)17CH3)@mSiO2) showed up to 80% uptake for hydrophobic drugs. However, a significant drawback was observed as most of the drugs were prone to uncontrollable release within 6 h. This challenge of premature drug release was successfully mitigated by effectively sealing the drug-loaded nanocarriers with a pH-sensitive lipid overlayer. The lipid-coated nanocarriers prolonged drug containment and sustained release up to 72 h, compared to 6 h for uncoated nanocarriers, thereby facilitating longer blood circulation times. Moreover, the shape and size of nanocarriers were found to influence both drug entrapment capacity and release behavior with cubic forms exhibiting superior loading capacity due to higher surface area and porosity. Additionally, it was observed that the molecular weight and chemical structure of the drug molecules played a crucial role in determining their uptake and release profiles. Furthermore, the influence of different morphologies of nanocarriers on cell uptake and cytotoxicity in immune cells was elucidated. These findings underscore the importance of nanocarrier morphology and drug properties to enhance loading capacities and controlled release profiles, for designing drug delivery systems tailored for hydrophobic drugs.

Release kinetics approach of stimuli-responsive mesoporous silica nanocarriers: pH-sensitive linker versus pH-sensitive framework

Silica-based stimuli-responsive nanomaterials have attracted significant attention in the field of drug delivery because they can achieve controlled release of anticancer drugs. For this, a gatekeeper is usually used, thus avoiding unwanted leakage at pH 7.4, while modulating the release under more acidic pH conditions in the tumor cell microenvironment. To optimize the efficiency of these nanostructures, it is crucial to study the release kinetics of anticancer drugs, predict their behavior, and modify the transport process mechanism. In the present study, we synthesized and characterized two types of pH-responsive mesoporous silica nanocarriers, which have transferrin conjugates on the surface serving as a gatekeeper. One nanocarrier was a conventional mesoporous silica nanoparticle (MSN) with transferrin attached through a pH-sensitive linker (MSN-Tf), while the other had a pH-sensitive diimine bridge in its framework, giving it degradable characteristic (dMSN-Tf). The use of conventional mathematical models and a three-parameter model that considers the drug-matrix interaction allowed the evaluation and elucidation of the different mechanisms involved in the kinetics of doxorubicin release from both materials at pH 7.4 and pH 5.0. The change in the kinetics of doxorubicin release from zero-order to first-order when it is in a degradable system such as dMSN-Tf, can be very useful for rapid drug delivery in acidic media such as inside cancer cells. Cell viability experiments in lung cancer cell lines A549 and H1299, showed enhanced anticancer activity by the nanomaterial with the pH-sensitive framework compared to the material that has a pH-sensitive linker. Overall, these findings provide important insights for optimizing the delivery of anticancer drugs.

Validation of Dual-Action Chemo-Radio-Labeled Nanocarriers with High Efficacy against Triple-Negative Breast Cancer.

Identification and selectivity of molecular targets with prolonged action for difficult-to-target cancer such as triple-negative breast cancer (TNBC) represent a persisting challenge in the precision delivery of therapeutics. In the quest to target undruggable sites, this study validates the bioavailability of polydopamine-sealed mesoporous silica nanocarriers (PDA-mSiO2) for in vivo drug delivery to TNBC. For controlled transport and release, the chemotherapeutic drug doxorubicin was encapsulated in mSiO2 nanocarriers coated with a PDA layer serving as a stimuli-responsive gatekeeper or seal. For unifying targeting and treatment modalities, these nanocarriers were covalently conjugated to a macrocyclic chelator (DOTA) and folate (FA-mSiO2.) that enabled incorporation of radionuclides and identification of FR Alpha (FolRα) receptors present on TNBC cells. The robust chemical design of FA- and DOTA-functionalized PDA-coated mSiO2 nanocarriers constitutes mild reaction conditions to avoid the loss of surface-bound molecules. The radiolabeling studies with the theranostic pair 68Ga and 177Lu showed quantitative trends for radiochemical efficacy and purity. Nanocarriers equipped with both radiolabels and affinity ligands were optimally stable when incubated with human serum for up to 120 h (177Lu), demonstrating hydrophilicity with a partition coefficient (log P) of -3.29 ± 0.08. Specifically, when incubated with TNBC cells, the cells received significant FA-mSiO2 carriers, demonstrating efficient carrier internalization and time-dependent uptake. Moreover, in vivo results visualize the retention of drug-filled carriers at the tumor sites for a long time, which holds promise for therapeutic studies. This research work demonstrates for the first time the successful dual conjugation of nanocarriers through the colocation of radionuclides and anticancer drugs that is promising for both live molecular imaging and enhanced therapeutic effect for TNBC.

Simple and biodegradable mesoporous silica nanocarriers for enhancing antitumor therapy through photochemical synergism.

The biosafety and degradability of nanocarriers have always been an important factor restricting their entry into the clinic. In this work, a new nano-system was prepared by coating the photothermal effect of dopamine-doped mesoporous silica nanoparticles with carboxymethyl chitin through electrostatic interaction, and is further anchored with folic acid on the surface for targeted delivery of anti-cancer the drug doxorubicin (DOX). The nano-system (DOX@PDA/MSN-CMCS-FA) is simply modified CMCS after being loaded with DOX and has good dispersibility, and the drug loading is 10.6%. In vitro release studies have shown that the release rate of PDA/MSN-CMCS-FA is 40% in pH 5.5. Effective degradation is debris in 14 d acidic environments. Due to the anti-infrared photothermal effects of PDA doping and DOX chemotherapy, the semi-lethal concentration (IC50) of nanoparticles (NPS) was 14.95μg/mL, which can inhibit tumor cell growth by photochemical synergistic treatment, and have certain degradation performance.

Preparation of Salicylic Acid-Functionalized Nanopesticides and Their Applications in Enhancing Salt Stress Resistance.

Soil salinization is one of the global ecological and environmental problems that are tremendously threatening to the sustainable development of agriculture and food supply. In this work, a facile strategy was proposed to enhance the salt stress resistance of plants by preparing salicylic acid (SA)-functionalized mesoporous silica nanocarriers loaded with emamectin benzoate (EB). The obtained nanopesticides demonstrated a particle size of less than 300 nm. As an endogenous plant hormone, the grafting of SA in this nanopesticide system improved the uptake and translocation of pesticides in cucumber plants by 145.06%, and the applications of such nanopesticides enhanced the salt stress resistance of plants. This phenomenon was accounted for by the SA-functionalized nanopesticides increasing the superoxide dismutase and peroxidase activities (640 and 175%, respectively) and reducing the malondialdehyde content (54.10%), correspondingly alleviating the accumulation of reactive oxygen species and cell damage in plants. The above results were also confirmed by Evans blue staining and NBT staining experiments on cucumber leaves. In addition, these nanopesticides exhibited high insecticidal toxicity, and they also demonstrated biosafety toward nontarget organisms due to their sustained release property. Therefore, this work developed a biosafe SA-functionalized nanopesticide system, and these newly developed nanopesticides have potential in the agricultural field for enhancing salt stress resistance of plants.

A novel oral biomimetic delivery system enhancing both the mucosal and systemic immunity of influenza virus vaccine

Oral vaccines hold great promise for preventing major infectious diseases, but their development is limited by various gastrointestinal tract (GIT) barriers and the low proportion of intestinal microfold (M) cells. Here, inspired by the specific absorption pathway of dietary fat, a novel bionic intestinal lymphatic delivery system based on large mesoporous silica nanoparticles (LMSN) was developed for oral delivery of H1N1 influenza split vaccine (SV). Encouragingly, LMSN with triglyceride biomimetic structure and encapsulated by double-end palmitic acid esterified PEG (PEG-DP), namely TGLMSN@PEG-DP, exhibited high intestinal epithelium permeability and excellent lymphatic targeting ability. Additionally, TGLMSN, which acting as both antigen carrier and adjuvant, significantly enhanced the ability of SV to stimulate dendritic cells maturation. The results demonstrated that TGLMSN@PEG-DP vigorously augmented SV-induced antigen-specific systemic and mucosal immunity, compared to oral SV alone. To our knowledge, this is the first study to customize mesoporous silica nanocarriers to load SV and deliver vaccines to mesenteric lymph nodes (MLNs) mainly through the intestinal epithelium cells (IECs) pathway rather than M cells route alone. This work will not only improve the existing influenza vaccination methods, but also open up a new avenue for the design of vaccines against pathogens infected via mucosal route.

Bioinspired hot-spot engineering strategy towards ultrasensitive SERS sandwich biosensor for bacterial detection

Surface-enhanced Raman spectroscopy (SERS) sandwich biosensors have received tremendous attention in early diagnosis of bacterial infections. However, efficiently engineering nanoscale plasmonic hots pots (HS) towards ultrasensitive SERS detection still remains challenging. Herein, we propose a bioinspired synergistic HS engineering strategy to construct ultrasensitive SERS sandwich bacterial sensor (named USSB), by coupling bioinspired signal module and plasmonic enrichment module to synergistically boost the number and intensity of HS. The bioinspired signal module is based on dendritic mesoporous silica nanocarrier (DMSN) loaded with plasmonic nanoparticles and SERS tag, while magnetic Fe3O4 nanoparticles coated with Au shell are employed in plasmonic enrichment module. We demonstrate that DMSN effectively shrank nanogaps between plasmonic nanoparticles to improve HS intensity. Meanwhile, plasmonic enrichment module contributed to plenty of additional HS inside and outside individual “sandwich”. Ascribing to the boosted number and intensity of HS, the constructed USSB sensor exhibits ultrahigh detection sensitivity (7 CFU/mL) and selectivity towards model pathogenic bacteria of Staphylococcus aureus. Remarkably, the USSB sensor enables fast and accurate bacterial detection in real blood samples of septic mice, achieving early diagnosis of bacterial sepsis. The proposed bioinspired synergistic HS engineering strategy opens up a new direction for constructing ultrasensitive SERS sandwich biosensors, and may promote their advancing applications in the early diagnosis and prognosis of devastating diseases.

Fabrication of badminton-like porous silica carriers and their application in drug release

Current research on silica-based drug delivery systems (DDS) mainly focuses on spherical silica nanocarriers, but asymmetric silica carriers display improving uptake efficiency. In this paper, asymmetric mesoporous silica (AMS) nanocarriers were designed and prepared by asymmetric modification. The AMS sample presents badminton-like structure with head of about 250 nm and tail length of 60–70 nm. Compared with spherical carriers, the AMS carriers displayed higher cell uptake efficiency. When doxorubicin (DOX) was loaded, hyaluronic acid (HA) molecules were used to block the loaded-drug. HA layer was easily degraded by endogenous hyaluronidase (HAase) or acidic environment. The obtained DOX@AMS-HA displayed pH/enzyme-triggered drug release.

Bacteria-responsive, Cell-recruitable, and osteoinductive nanocomposite microcarriers for intelligent bacteriostasis and accelerated tissue regeneration

Repairing alveolar bone defects with chronic periodontitis is a major clinical challenge, since the periodontitis causes the intermittent bacteria invasion to irreversibly aggravates the degeneration of alveolar bones. To deal with the challenge, a kind of novel microcarriers with excellent abilities of responding to alkaline phosphatase (ALP) to intelligently eliminate the bacteria and promoting the recruitment and osteogenic differentiation of endogenous stem cells are developed. Mesoporous silica nanocarriers that chemically fix the polyethylene glycol-modified amoxicillin (PEG-AML) through the phosphoester groups and electrostatically adsorb the aspirin (ASP) are first prepared. The nanocarriers are then dispersed in a chitosan solution to prepare the bacteria-responsive, cell-recruitable, and osteoinductive nanocomposite microcarriers. When being stimulated by ALP that are secreted by the bacteria, phosphoester groups of microcarriers are cleaved, and PEG-AML are delivered on demand to well achieve the goal of intelligent bacteriostasis. The microcarriers slowly release the ASP to promote the recruitment and osteogenic differentiation of endogenous stem cells. At 8 weeks post-implantation, the microcarriers facilitate the repair of alveolar bone defects with periodontitis. The blood vessels in the neo-generated alveolar bones grow well. Due to the appropriate degradation time and excellent antibacterial ability of microcarriers, the microcarriers exhibit a better therapeutic efficacy than the standard clinical products (Geistlich Bio-Oss®), providing a new insight into the cure of alveolar bone defects with periodontitis.

Ordered mesoporous silica nanocarriers: An innovative paradigm and a promising therapeutic efficient carrier for delivery of drugs

Ordered mesoporous silica nanocarriers: An innovative paradigm and a promising therapeutic efficient carrier for delivery of drugs

Repurposing Anthelmintics: Rafoxanide- and Copper-Functionalized SBA-15 Carriers against Methicillin-Resistant Staphylococcus aureus.

The development of materials that can more efficiently administer antimicrobial agents in a controlled manner is urgently needed due to the rise in microbial resistance to traditional antibiotics. While new classes of antibiotics are developed and put into widespread usage, existing, inexpensive compounds can be repurposed to fight bacterial infections. Here, we present the synthesis of amine-functionalized SBA-15 mesoporous silica nanomaterials with physisorbed rafoxanide (RFX), a commonly used salicylanilide anthelmintic, and anchored Cu(II) ions that exhibit enhanced antimicrobial efficacy against the pathogenic bacterium Staphylococcus aureus. The synthesized nanomaterials are structurally characterized by a combination of physicochemical, thermal, and optical methods. Additionally, release studies are carried out in vitro to determine the effects of pH and the synthetic sequence used to produce the materials on Cu(II) ion release. Our results indicate that SBA-15 mesoporous silica nanocarriers loaded with Cu(II) and RFX exhibit 10 times as much bactericidal action against wild-type S. aureus as the nanocarrier loaded with only RFX. Furthermore, the synthetic sequence used to produce the nanomaterials could significantly affect (enhance) their bactericidal efficacy.

Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment. Herein, a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination, on-demand adipose tissue regeneration and effective infection inhibition. The hydrogel consisted of thiol groups ended polyethylene glycol (SH-PEG-SH) and doxorubicin encapsulated mesoporous silica nanocarriers (DOX@MSNs) double crosslinked hyaluronic acid (HA) after loading of antibacterial peptides (AP) and adipose-derived stem cells (ADSCs). A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release, meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs, which contributed to the selective chemotherapy in tumor cells with over-expressed esterase. The bond cleavage between MSNs and HA would also cause the swelling of the hydrogel, which not only provide sufficient space for the growth of ADSCs, but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy, resulting in the on-demand regeneration of adipose tissue. Moreover, the sustained release of AP could be simultaneously triggered along with the size change of hydrogel, which further avoided bacterial infection to promote tissue regeneration.

Chiral Nanosilica Drug Delivery Systems Stereoselectively Interacted with the Intestinal Mucosa to Improve the Oral Adsorption of Insoluble Drugs.

Chiral nanoparticles (NPs) with nanoscale rough surfaces have enormous application prospects in drug delivery. However, the stereoselective interactions between the chiral NPs and biosurfaces remain challenging and mysterious. Herein, we designed mesoporous silica nanocarriers (l/d/dl-TA-PEI@CMSN) exhibiting the same structural parameters (hydrophilic, electroneutral, spherical NPs, ∼120 nm) but different geometrical chirality as oral nanodrug delivery systems (Nano-DDS) for insoluble drugs nimesulide (NMS) and ibuprofen (IBU) and demonstrated their stereoselective interactions with the intestinal mucosa, that is, l-TA-PEI@CMSN as well as Nano-DDS in the l-configuration displayed apparent superior behaviors in multiple microprocesses associated with oral adsorption, including adhesion, penetration, adsorption, retention and uptake, causing by the stereomatching between the chiral mesostructures of NPs and the inherent chiral topologies of the biosurfaces. As hosting systems, l/d/dl-TA-PEI@CMSN effectively incorporated drugs in amorphous states and helped to overcome the stability, solubility and permeability bottlenecks of drugs. Subsequently, Nano-DDS in the l-configuration (including IBU/l-TA-PEI@CMSN and NMS/d-TA-PEI@CMSN owing to a chiral inversion) showed higher oral delivery efficiency of NMS and IBU evidenced by the larger relative bioavailability (1055.06% and 583.17%, respectively) and stronger anti-inflammatory and analgesic effects. In addition, l/d/dl-TA-PEI@CMSN were stable, nonirritative, biocompatible and biodegradable, benefiting for their clinical applications. These findings provided insights into the rational design of functionalized Nano-DDS and contributed to the further knowledge in the field of chiral pharmaceutical science.

Investigation of the interaction between the functionalized mesoporous silica nanocarriers and bovine serum albumin via multi-spectroscopy

It is well known that the physicochemical properties of nanocarriers, which are closely related to the surface modification of nanoparticles, have crucial impacts on their biological effects. Herein, the interaction between functionalized degradable dendritic mesoporous silica nanoparticles (DDMSNs) and bovine serum albumin (BSA) was investigated for probing into the nanocarriers’ potential toxicity using multi-spectroscopy such as ultraviolet/visible (UV/Vis), synchronous fluorescence, Raman and circular dichroism (CD) spectroscopy. BSA, owing to its structural homology and high sequence similarity with HSA, was employed as the model protein to study the interactions with DDMSNs, amino-modified DDMSNs (DDMSNs-NH2) and hyaluronic acid (HA) coated nanoparticles (DDMSNs-NH2-HA). It was found that the static quenching behavior of DDMSNs-NH2-HA to BSA was accompanied by an endothermic and hydrophobic force-driven thermodynamic process, which was confirmed by fluorescence quenching spectroscopic studies and thermodynamic analysis. Furthermore, the conformational variations of BSA upon interaction with nanocarriers were observed by combination of UV/Vis, synchronous fluorescence, Raman and CD spectroscopy. The microstructure of amino residues in BSA changed due to the existence of nanoparticles, for example, the amino residues and hydrophobic groups exposed to microenvironment and the alpha helix (α-helix) content of BSA decreased. Specially, through thermodynamic analysis, the diverse binding modes and driving forces between nanoparticles and BSA were discovered because of different surface modifications on DDMSNs, DDMSNs-NH2 and DDMSNs-NH2-HA. We believe that this work can promote the interpretation of mutual impact between nanoparticles and biomolecules, which will be in favor of predicting the biological toxicity of nano-DDS and engineering functionalized nanocarriers.

High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery.

The main cause of subretinal neovascularisation in wet age-related macular degeneration (AMD) is an abnormal expression in the retinal pigment epithelium (RPE) of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues that could be overcome by encapsulating anti-VEGF drugs in suitable nanocarriers, thus providing better penetration, higher retention times, and sustained release. In this work, the ability of large pore mesoporous silica nanoparticles (LP-MSNs) to transport and protect nucleic acid molecules is exploited to develop an innovative LP-MSN-based nanosystem for the topical administration of anti-VEGF siRNA molecules to RPE cells. siRNA is loaded into LP-MSN mesopores, while the external surface of the nanodevices is functionalised with polyethylenimine (PEI) chains that allow the controlled release of siRNA and promote endosomal escape to facilitate cytosolic delivery of the cargo. The successful results obtained for VEGF silencing in ARPE-19 RPE cells demonstrate that the designed nanodevice is suitable as an siRNA transporter.

Glutathione-responsive mesoporous silica nanocarriers for chemo–photothermal–photodynamic therapy of cancer

Glutathione-responsive mesoporous silica nanocarriers for chemo–photothermal–photodynamic therapy of cancer

Preparation of mesoporous silica nanocarriers targeting glucose-6-phosphate isomerase inhibition and application in the treatment of rheumatoid arthritis.

Glucose 6-phosphate isomerase (G6PI) is an indicator to assist in diagnosis of rheumatoid arthritis (RA) and monitor the disease. It also plays a key role in proliferating RA synovial tissues, pannus formation, and invasion and destruction of articular cartilage. In this study, we synthesized nanoparticles targeting G6PI (siG6PI-MSN) using mesoporous silica nanocarriers (MSN) and small interfering RNA (siRNA), followed by identifying the characteristics and functions, and preliminarily exploring their application in the treatment of RA in vivo with a type II collagen-induced arthritis (CIA) rat model. It showed that the synthetic functionalized carrier had a regular pore structure and a specific volume and surface area. No obvious hemolysis or toxicity of the carrier was found when its concentration was below 100 µg/ml. Cytological results in vitro suggested that siG6PI-MSN significantly inhibited G6PI expression and reduced the ability of proliferation, migration, and invasion of FLSs, compared with the siNC-MSN group. In vivo results in the CIA rat model showed that the arthritis index and degree of joint swelling among rats in the siG6PI-MSN-treatment group were significantly lower than those in the control group. Moreover, the number of FLSs in Synovium and the levels of TNF α and IL-1 β were also significantly decreased in the siG6PI-MSN group. Histopathology of the synovial tissue and cartilage revealed siG6PI-MSN treatment significantly reduced the pathological manifestations of arthritis. In conclusion, siG6PI-MSN effectively suppresses the proliferation and invasive growth of synovial tissue and improve joint swelling and inflammatory infiltration, thereby preventing joint damage in RA. This carrier may be a new therapeutic measure for RA, with potential social and economic benefits.

PH-responsive and targeted delivery of chrysin via folic acid-functionalized mesoporous silica nanocarrier for breast cancer therapy

Cancer is a disease of global importance. In order to mitigate conventional chemotherapy-related side effects, phytochemicals with inherent anticancer efficacy have been opted. However, the use of nanotechnology is essential to enhance the bioavailability and therapeutic efficacy of these phytochemicals. Herein, we have formulated folic acid conjugated polyacrylic acid capped mesoporous silica nanoparticles (∼47.6 nm in diameter) for pH-dependent targeted delivery of chrysin to breast cancer (MCF-7) cells. Chrysin loaded mesoporous silica nanoparticles (Chr- mSiO2@PAA/FA) have been noted to induce apoptosis in MCF-7 cells through oxidative insult and mitochondrial dysfunction with subsequent G1 arrest. Further, in tumor bearing mice, intravenous incorporation of Chr-mSiO2@PAA/FA has been noticed to enhance the anti-neoplastic effects of chrysin via tumor site-specific accumulation. Enhanced cytotoxicity of chrysin contributed towards in vivo tumor regression, restoration of normalized tissue architecture and maintenance of healthy body weight. Besides, no serious systemic toxicity was manifested in response to Chr-mSiO2@PAA/FA administration in vivo. Thus, the study evokes about the anticancer potentiality of chrysin and its increased therapeutic activity via incorporation into folic acid conjugated mesoporous silica nanoparticles, which may hold greater impact in field of future biomedical research.