Journal: Expert opinion on drug delivery

Article Title: Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

doi: 10.1080/17425247.2019.1598375

Figure Lengend Snippet: Transmission electron microscopy of several kinds of MSNs for different biomedical applications, showing (1st row) center-radial porosity (MSNR) with different particle and pore size (2-12 nm); (2nd row) longitudinal or 2D-hexagonal structure (MSNL) with different particle size (150-50 nm); (3rd row) MSNs coated with different inorganic nanoparticles such as gold nanorods (MSN-AuNR); gold nanoparticles (MSN-AuNPs), silver nanoparticles (MSN-AgNPs) and magnetite nanoparticles (MSN-Fe3O4); (4th row) core@shell structure with hydroxyapatite nanorods (HANR), gold nanorods (AuNR) and magnetite nanoparticles (Fe3O4) as core.

Article Snippet: The cytochrome c (Cyt c)/DOX dual therapy is achieved by immobilizing Cyt c onto the surface of yolk-shell MSNs (YMSNs) via H 2 O 2 -liable boronic ester bonds and further modifying the nanocarrier with lactic acid units to confer as well selective tumor targeting against liver cancer cells.

Techniques: Transmission Assay, Electron Microscopy, Pore Size

Journal: Expert opinion on drug delivery

Article Title: Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

doi: 10.1080/17425247.2019.1598375

Figure Lengend Snippet: Main factors influencing MSNs biodistribution and its accumulation in defense organs.

Article Snippet: The cytochrome c (Cyt c)/DOX dual therapy is achieved by immobilizing Cyt c onto the surface of yolk-shell MSNs (YMSNs) via H 2 O 2 -liable boronic ester bonds and further modifying the nanocarrier with lactic acid units to confer as well selective tumor targeting against liver cancer cells.

Techniques:

Journal: Expert opinion on drug delivery

Article Title: Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

doi: 10.1080/17425247.2019.1598375

Figure Lengend Snippet: (Top) Schematic representation showing the more representative approaches described up to date, PEGylation and zwitterionization, to increase the resistance of non-specific protein adsorption and the stealthy to the macrophages. (Bottom) Confocal microscopy studies showing the macrophage-uptake of different MSN-type systems (bare MSNs, MSN-Zwitter and PEGylated MSN). The staining corresponds to cell-nuclei (DAPI, blue), cell membrane and cytoskeleton (phalloidin, red) and nanoparticles (fluorescein, green). Internalized nanoparticles are highlighted with yellow arrows, while those located in the outer area are marked with white arrows. Scale bar: 5 μm.

Article Snippet: The cytochrome c (Cyt c)/DOX dual therapy is achieved by immobilizing Cyt c onto the surface of yolk-shell MSNs (YMSNs) via H 2 O 2 -liable boronic ester bonds and further modifying the nanocarrier with lactic acid units to confer as well selective tumor targeting against liver cancer cells.

Techniques: Adsorption, Confocal Microscopy, Staining, Membrane

Journal: Expert opinion on drug delivery

Article Title: Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

doi: 10.1080/17425247.2019.1598375

Figure Lengend Snippet: Comprehensive list of active targeting ligands employed for favoring uptake of MSNs onto different cell lines.

Article Snippet: The cytochrome c (Cyt c)/DOX dual therapy is achieved by immobilizing Cyt c onto the surface of yolk-shell MSNs (YMSNs) via H 2 O 2 -liable boronic ester bonds and further modifying the nanocarrier with lactic acid units to confer as well selective tumor targeting against liver cancer cells.

Techniques: Derivative Assay

Journal: Expert opinion on drug delivery

Article Title: Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

doi: 10.1080/17425247.2019.1598375

Figure Lengend Snippet: Different strategies to provide active targeting to MSNs.

Article Snippet: The cytochrome c (Cyt c)/DOX dual therapy is achieved by immobilizing Cyt c onto the surface of yolk-shell MSNs (YMSNs) via H 2 O 2 -liable boronic ester bonds and further modifying the nanocarrier with lactic acid units to confer as well selective tumor targeting against liver cancer cells.

Techniques:

Journal: Expert opinion on drug delivery

Article Title: Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

doi: 10.1080/17425247.2019.1598375

Figure Lengend Snippet: Schematic representation of internal or endogenous stimuli to the pathological microenvironments (pH, redox, enzymes and small molecules) and external or exogenous (magnetic field, light, temperature and ultrasounds) stimuli that can be used to trigger on demand drug release from MSNs.

Article Snippet: The cytochrome c (Cyt c)/DOX dual therapy is achieved by immobilizing Cyt c onto the surface of yolk-shell MSNs (YMSNs) via H 2 O 2 -liable boronic ester bonds and further modifying the nanocarrier with lactic acid units to confer as well selective tumor targeting against liver cancer cells.

Techniques:

Journal: Expert opinion on drug delivery

Article Title: Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

doi: 10.1080/17425247.2019.1598375

Figure Lengend Snippet: Reviewed stimuli employed for drug delivery using MSNs.

Article Snippet: The cytochrome c (Cyt c)/DOX dual therapy is achieved by immobilizing Cyt c onto the surface of yolk-shell MSNs (YMSNs) via H 2 O 2 -liable boronic ester bonds and further modifying the nanocarrier with lactic acid units to confer as well selective tumor targeting against liver cancer cells.

Techniques: Solubility, Sequencing, Concentration Assay, Binding Assay, Polymer, Transformation Assay, Irradiation, Generated, Membrane

Journal: Advanced Science

Article Title: Nanorepairers Rescue Inflammation‐Induced Mitochondrial Dysfunction in Mesenchymal Stem Cells

doi: 10.1002/advs.202103839

Figure Lengend Snippet: Schematic representation of the structure and function of METP NPs as well as how si β ‐catenin loaded METP NPs (METP/si β ‐catenin) sweep dysfunctional mitochondria and restore the function of mitochondria and MSCs. Chronic inflammation leads to excess Ca 2+ transfer to mitochondria, which causes mitochondria calcium overload and the further damage of mitochondrial. Moreover, the damaged mitochondria continuously accumulate in MSCs due to the inhibition of mitophagy by the activation of Wnt/ β ‐catenin pathway under chronic inflammation condition (inhibiting the transfer from LC3II to LC3I for autophagosome formation in PDLSCs while decreasing the expression of pink1 and parkin to initiate mitophagy in BMMSCs), which impair the function of MSCs. Intracellular microenvironments (esterase and low pH)‐responsive nanoparticles are devised to capture Ca 2+ around mitochondria in MSCs for regulating its mitochondria calcium flux against dysfunction of mitochondria, as well as to deliver si β ‐catenin in MSCs to inhibit its Wnt/ β ‐catenin pathway for regulating mitophagy of dysfunctional mitochondria. The precision‐engineered nanoparticles, termed METP NPs, involve an amino functionalized mesoporous silica nanoparticles (MSN‐NH2) core as nanocarrier for si β ‐catenin loading and pH triggered si β ‐catenin release in targeted MSCs, an ethylene glycol tetraacetic acid (EGTA)/TPP composite shell as mitochondria‐targeted Ca 2+ trapper, as well as a PEG corona connected with EGTA segments via ester bond. The ester bond would be cleaved by esterase to detach PEG corona after the endocytosis of MSCs, resulting in the activation of EGTA only in targeted MSCs, which was designed to avoid the disturbance of unexpected Ca 2+ capture in the extracellular matrix.

Article Snippet: Precision‐engineered nanoparticles involve a positively charged mesoporous silica nanoparticle (TMA‐MSN) core as a nanocarrier for siRNA loading and pH‐triggered siRNA release in targeted MSCs, an ethylene glycol tetraacetic acid (EGTA, calcium chelator)/triphenylphosphine (TPP, mitochondrial targeting agent) composite shell to trap mitochondria‐related Ca 2+ , and a polyethylene glycol (PEG) corona connected with EDTA segments via ester bonds.

Techniques: Inhibition, Activation Assay, Expressing

Journal: Chemical Society Reviews

Article Title: Engineering mesoporous silica nanoparticles for drug delivery: where are we after two decades?

doi: 10.1039/d1cs00659b

Figure Lengend Snippet: Multifunctionality in MSNs for bacterial infection treatment. Targeting ligands towards bacteria and/or biofilm (blue arrows) can decorate the external surface. Antimicrobial drugs (antibiotics) and/or antibiofilm agents (proteins and peptides) can be either adsorbed into the mesopores or else grafted to the silica walls. Stimuli-responsive pore capping agents (red nanocaps) can close the pores to prevent premature cargo release. The presence of internal ( e.g. bacteria, pH, enzymes, redox potential) or external ( e.g. heat, light, alternating magnetic fields (AMF)) stimuli (orange rays) provokes pore opening and cargo release. Antimicrobial metal NPs (M) and ions (M n + ) can be embedded into the mesoporous structure or grafted to the outer surface of MSNs. Biocompatible hydrophilic polymers (in orange) can be grafted to the external surface to provide “stealth” properties. External grafting of organic groups (R) permits tuning the surface charge. Magnetic NPs and fluorescent molecules (green stars) can be also incorporated.

Article Snippet: The results of both studies demonstrated that it is possible to avoid the limitations of BMP treatments by loading these molecules into a nanovector such as MSNs.

Techniques: Infection, Bacteria

Journal: Nanomaterials

Article Title: Redox-Responsive Mesoporous Silica Nanoparticles for Cancer Treatment: Recent Updates

doi: 10.3390/nano11092222

Figure Lengend Snippet: ( a ) Schematic representation of the synthesis of the enzyme- and redox-responsive MSNs. ( b ) Schematic representation of the mechanism of action. The overexpressed metalloproteinases can partially degrade the gelatin coating, which can be completely degraded due to the action of GSH. Reproduced with permission from . Copyright Elsevier, 2019.

Article Snippet: For instance, albumin or myoglobin can be employed to prevent premature drug release by attaching them to the MSNs using diselenide bonds, obtaining a nanocarrier highly responsive to both GSH and H 2 O 2 [ ].

Techniques:

Journal: Nanomaterials

Article Title: Redox-Responsive Mesoporous Silica Nanoparticles for Cancer Treatment: Recent Updates

doi: 10.3390/nano11092222

Figure Lengend Snippet: ( A ) TEM micrographs of MSNs and MSNs coated with Au NPs. ( B ) Release profiles at different pHs, in the presence or absence of GSH, and upon application or not of NIR light. The highest drug release is obtained when both GSH and NIR light are applied. Adapted with permission from . Copyright Elsevier, 2017.

Article Snippet: For instance, albumin or myoglobin can be employed to prevent premature drug release by attaching them to the MSNs using diselenide bonds, obtaining a nanocarrier highly responsive to both GSH and H 2 O 2 [ ].

Techniques:

Journal: Nanomaterials

Article Title: Redox-Responsive Mesoporous Silica Nanoparticles for Cancer Treatment: Recent Updates

doi: 10.3390/nano11092222

Figure Lengend Snippet: Representative example of the biodegradation by GSH of bridged (here denoted as MONs) vs. conventional MSNs. The different NPs were incubated in SBF solution in the presence or absence of 10 mM of GSH. As observed, conventional MSNs were nearly unaffected after 7 days, irrespective of the presence of GSH, whereas those containing disulfide bonds broke into tiny fragments in the reductive environment. Reproduced with permission from . Copyright Elsevier, 2018.

Article Snippet: For instance, albumin or myoglobin can be employed to prevent premature drug release by attaching them to the MSNs using diselenide bonds, obtaining a nanocarrier highly responsive to both GSH and H 2 O 2 [ ].

Techniques: Incubation

Journal: Nanomaterials

Article Title: Redox-Responsive Mesoporous Silica Nanoparticles for Cancer Treatment: Recent Updates

doi: 10.3390/nano11092222

Figure Lengend Snippet: ( A ) Schematic representation of bridged, biodegradable MSNs functionalized with boronophenylalanine on the surface for BNCT. ( B ) The NPs degraded almost completely after 7 days in the presence of GSH. ( C ) Great tumor reduction was observed in the group of irradiated NPs. Adapted with permission from . Copyright MDPI, 2021.

Article Snippet: For instance, albumin or myoglobin can be employed to prevent premature drug release by attaching them to the MSNs using diselenide bonds, obtaining a nanocarrier highly responsive to both GSH and H 2 O 2 [ ].

Techniques: Irradiation

Journal: Pharmaceutics

Article Title: Combinatorial Therapeutic Approaches with Nanomaterial-Based Photodynamic Cancer Therapy

doi: 10.3390/pharmaceutics14010120

Figure Lengend Snippet: Preclinical studies on inorganic nanoparticles for codelivery in PDT plus chemotherapy.

Article Snippet: IR820 , TPZ , Glutathione decomposable MSNs (GMONs) , Biocompatibility and stability; GSH/enzyme dual-responsive; tumor targeting by HA , 4T1 breast tumor mouse model , Enhanced tumor inhibition rate of dual-loaded nanohybrids was up to 76% under NIR laser irradiation in vivo, due to PDT-induced hypoxia resulting in improved TPZ effects , [ ] .

Techniques: Inhibition, In Vitro, In Vivo, Imaging, Membrane, Irradiation, Solubility, Drug discovery, Staining, Binding Assay, Activity Assay, Polymer, TUNEL Assay, Calcium Carbonate, Dispersion, CCK-8 Assay

Journal: International Journal of Molecular Sciences

Article Title: Preclinical Assessment of ADAM9-Responsive Mesoporous Silica Nanoparticles for the Treatment of Pancreatic Cancer

doi: 10.3390/ijms241310704

Figure Lengend Snippet: Paclitaxel-loaded ADAM9-MSNs evoke neurotoxicity and bone marrow toxicity in preclinical models in vitro. IC50 curve in PANC-1 ( A ) and SH-SY5Y ( C ) cells after 72 h of free paclitaxel administration (data modified from a previous publication ). Cytotoxicity of paclitaxel-loaded ADAM9-MSNs in PANC-1 ( B ) and SH-SY5Y ( D ) cells after 72 h. Data are shown as the mean of one representative experiment with n = 6. Results are normalized to untreated controls. Microscopic images resembling diverse bone-marrow-derived colonies from representative colony-forming assays ( E ). Cytotoxicity of free paclitaxel and paclitaxel-loaded ADAM9-MSNs on bone marrow cells from colony-forming assays after 7 days. Data are shown as the mean of one representative experiment with n = 3. Levels of significance: ** p < 0.01 and *** p < 0.001.

Article Snippet: In summary, 1 mg of MSNs was added to 10 mg/mL paclitaxel (>99.5%, LC Laboratories, Woburn, ON, Canada) and incubated at 37 °C and 1200 rpm for 1.5 h. Loaded MSNs were centrifuged to measure the UV absorbance of the supernatant and determine the amount of loaded paclitaxel.

Techniques: In Vitro, Modification, Derivative Assay

Journal: International Journal of Molecular Sciences

Article Title: Preclinical Assessment of ADAM9-Responsive Mesoporous Silica Nanoparticles for the Treatment of Pancreatic Cancer

doi: 10.3390/ijms241310704

Figure Lengend Snippet: MSNs with a modified ADAM9 linker have increased PDAC specificity and reduced general toxicity. ( A ) Expression levels of proteases capable of cleaving the ADAM9 linker. Data were extracted from publicly available gene expression datasets (GSE36133, GSE57083, GSE46903, and E-MTAB-783). ( B ) Molecular structure of modified ADAM9 linker (OPT linker). ( C ) Transmission electron microscopic images of peptide–biotin-coupled MSNs. ( D ) Fourier transform infrared spectra of MSNs, several modified intermediates, and final products OPT and uncleavable OPT-MSNs. ( E ) Cytotoxicity of paclitaxel-loaded OPT and uncleavable OPT-MSNs in PANC-1 cells after 72 h ( n = 12). ( F ) Cytotoxicity of paclitaxel-loaded OPT-MSNs in Capan-2 cells ( n = 12) and SH-SY5Y cells (( G ), n = 12) after 72 h and in bone marrow cells (( H ), n = 3) after 7 days. Data are normalized to untreated controls. Levels of significance: ns = not significant, * p < 0.05 and **** p < 0.0001.

Article Snippet: In summary, 1 mg of MSNs was added to 10 mg/mL paclitaxel (>99.5%, LC Laboratories, Woburn, ON, Canada) and incubated at 37 °C and 1200 rpm for 1.5 h. Loaded MSNs were centrifuged to measure the UV absorbance of the supernatant and determine the amount of loaded paclitaxel.

Techniques: Modification, Expressing, Gene Expression, Transmission Assay, Fourier Transform Infrared Spectroscopy

Journal: International Journal of Molecular Sciences

Article Title: Preclinical Assessment of ADAM9-Responsive Mesoporous Silica Nanoparticles for the Treatment of Pancreatic Cancer

doi: 10.3390/ijms241310704

Figure Lengend Snippet: Paclitaxel-loaded OPT-MSNs reduce neutropenia and organ damage but show no antitumor effect in vivo. ( A ) Toxicity of paclitaxel-loaded OPT-MSNs in KP2 cells 72 h after administration ( n = 12). ( B ) Weight of mice during the experiment. ( C ) Tumor volume (mm 3 ) plotted over time. Data analysis was complicated by the fast-growing nature and ulcerative properties of KP2 cells, causing the sacrificing of 16 mice before the end of the experiment because they met the criteria set as humane end points. Both ulceration and reaching a tumor size of >1.5 cm 3 led to the killing of eight mice, and two mice reached both humane end points simultaneously. ( D ) Blood leukocyte counts at sacrifice. Plasma LDH ( E ), ALAT ( F ), and creatinine ( G ) levels as measured by HPLC following standardized clinical guidelines of the AUMC. Levels of significance: * p < 0.05 and *** p < 0.001.

Article Snippet: In summary, 1 mg of MSNs was added to 10 mg/mL paclitaxel (>99.5%, LC Laboratories, Woburn, ON, Canada) and incubated at 37 °C and 1200 rpm for 1.5 h. Loaded MSNs were centrifuged to measure the UV absorbance of the supernatant and determine the amount of loaded paclitaxel.

Techniques: In Vivo, Clinical Proteomics