scholarly journals Targeted Nano-Drug Delivery of Colchicine against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 144 ◽  
Author(s):  
Khaled AbouAitah ◽  
Heba A. Hassan ◽  
Anna Swiderska-Sroda ◽  
Lamiaa Gohar ◽  
Olfat G. Shaker ◽  
...  

Antimitotics are important anticancer agents and include the natural alkaloid prodrug colchicine (COL). However, a major challenge of using COL as an anticancer drug is its cytotoxicity. We developed a novel drug delivery system (DDS) for COL using mesoporous silica nanoparticles (MSNs). The MSNs were functionalized with phosphonate groups, loaded with COL, and coated with folic acid chitosan-glycine complex. The resulting nanoformulation, called MSNsPCOL/CG-FA, was tested for action against cancer and normal cell lines. The anticancer effect was highly enhanced for MSNsPCOL/CG-FA compared to COL. In the case of HCT116 cells, 100% inhibition was achieved. The efficiency of MSNsPCOL/CG-FA ranked in this order: HCT116 (colon cancer) > HepG2 (liver cancer) > PC3 (prostate cancer). MSNsPCOL/CG-FA exhibited low cytotoxicity (4%) compared to COL (~60%) in BJ1 normal cells. The mechanism of action was studied in detail for HCT116 cells and found to be primarily intrinsic apoptosis caused by an enhanced antimitotic effect. Furthermore, a contribution of genetic regulation (metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1), and microRNA (mir-205)) and immunotherapy effects (angiopoietin-2 (Ang-2 protein) and programmed cell death protein 1 (PD-1) was found. Therefore, this study shows enhanced anticancer effects and reduced cytotoxicity of COL with targeted delivery compared to free COL and is a novel method of developing cancer immunotherapy using a low-cost small-molecule natural prodrug.

Mesoporous silica nanoparticles (MSNs) have been attracting great attention for the potential biomedical applications in the last decades. Due to the unique properties, such as tunable mesoporous structure, huge surface area, large pore volume, as well as the functional ability of surface, MSNs exhibit high loading capacity for therapeutic active pharmaceutical ingredients (APIs) and controllable release behavior. In this review, the applications of MSNs in pharmaceutics improving the bioavailability, reducing toxicity of loaded drugs, increasing cellular targeted delivery ability and recent advances in drug delivery are summarized.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3082 ◽  
Author(s):  
Wei Liu ◽  
Fan Wang ◽  
Yongchao Zhu ◽  
Xue Li ◽  
Xiaojing Liu ◽  
...  

Targeted drug delivery to colon cancer cells can significantly improve the efficiency of treatment. We firstly synthesized carboxyl-modified mesoporous silica nanoparticles (MSN–COOH) via two-step synthesis, and then developed calcium leucovorin (LV)-loaded carboxyl-modified mesoporous silica nanoparticles based on galactosylated chitosan (GC), which are galectin receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), nitrogen sorption, and dynamic light scattering (DLS). Drug release properties and drug loading capacity were determined by ultraviolet spectrophotometry (UV). LV@MSN–COOH/GC had a high LV loading and a drug loading of 18.07%. In vitro, its release, mainly by diffusion, was sustained release. Cell experiments showed that in SW620 cells with the galectin receptor, the LV@MSN–COOH/GC metabolized into methyl tetrahydrofolic acid (MTHF) and 5-fluorouracil (5-FU)@MSN–NH2/GC metabolized into FdUMP in vivo. MTHF and 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) had combined inhibition and significantly downregulated the expression of thymidylate synthase (TS). Fluorescence microscopy and flow cytometry experiments show that MSN–COOH/GC has tumor cell targeting, which specifically recognizes and binds to the galectin receptor in tumor cells. The results show that the nano-dosing system based on GC can increase the concentrations of LV and 5-FU tumor cells and enhance their combined effect against colon cancer.


2020 ◽  
Vol 58 (1) ◽  
pp. 39 ◽  
Author(s):  
Ngoc Tram Nguyen Thi ◽  
Dai Hai Nguyen

Mesoporous silica nanoparticles (MSNs) have attracted significant attention from researchers thanks to their high surface area and pore volume, which can increase drug loading capacity. Moreover, MSNs, with their biocompatibility and ease of surface functionalization, are seen as potential drug delivery system. However, the loading of drug into MSNs system still needs further improvement. In this study, hollow mesoporous silica nanoparticles (HMSNs) were fabricated in order to increase the drug loading capacity of nanosilica materials. The synthesized HMSNs possessed inner hollow cores that could remarkably raise the total pore volume and thus improve the capacity for cargo loading. HMSNs were synthesized according to the hard-template method with three main steps: (1) forming of solid SiO2 nanoparticles as templates, (2) forming of core-shell structure by coating MSN layers onto the templates, and (3) forming of hollow core structure by etching away the solid template. The HMSNs product was characterized by TEM, XRD, TGA and FTIR. In addition, drug loading capacity of the material was evaluated with doxorubicin as model drug. The results indicated remarkable improvement in drug loading capacity, compared to MSN sample. Cell assays on cancer lines showed high biocompatibility. These results demonstrated the potential of HMSNs in the delivery of anticancer agents.


2017 ◽  
Vol 3 (12) ◽  
pp. 3376-3385 ◽  
Author(s):  
Prateek Srivastava ◽  
Sumit Kumar Hira ◽  
Divesh Narayan Srivastava ◽  
Uttam Gupta ◽  
Pradip Sen ◽  
...  

2020 ◽  
Vol 20 (11) ◽  
pp. 1001-1016
Author(s):  
Sandra Ramírez-Rave ◽  
María Josefa Bernad-Bernad ◽  
Jesús Gracia-Mora ◽  
Anatoly K. Yatsimirsky

Hybrid materials based on Mesoporous Silica Nanoparticles (MSN) have attracted plentiful attention due to the versatility of their chemistry, and the field of Drug Delivery Systems (DDS) is not an exception. MSN present desirable biocompatibility, high surface area values, and a well-studied surface reactivity for tailoring a vast diversity of chemical moieties. Particularly important for DDS applications is the use of external stimuli for drug release. In this context, light is an exceptional alternative due to its high degree of spatiotemporal precision and non-invasive character, and a large number of promising DDS based on photoswitchable properties of azobenzenes have been recently reported. This review covers the recent advances in design of DDS using light as an external stimulus mostly based on literature published within last years with an emphasis on usually overlooked underlying chemistry, photophysical properties, and supramolecular complexation of azobenzenes.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 844
Author(s):  
Thorben Fischer ◽  
Inga Winter ◽  
Robert Drumm ◽  
Marc Schneider

The transport of macromolecular drugs such as oligonucleotides into the lungs has become increasingly relevant in recent years due to their high potency. However, the chemical structure of this group of drugs poses a hurdle to their delivery, caused by the negative charge, membrane impermeability and instability. For example, siRNA to reduce tumour necrosis factor alpha (TNF-α) secretion to reduce inflammatory signals has been successfully delivered by inhalation. In order to increase the effect of the treatment, a co-transport of another anti-inflammatory ingredient was applied. Combining curcumin-loaded mesoporous silica nanoparticles in nanostructured cylindrical microparticles stabilized by the layer-by-layer technique using polyanionic siRNA against TNF-α was used for demonstration. This system showed aerodynamic properties suited for lung deposition (mass median aerodynamic diameter of 2.85 ± 0.44 µm). Furthermore, these inhalable carriers showed no acute in vitro toxicity tested in both alveolar epithelial cells and macrophages up to 48 h incubation. Ultimately, TNF-α release was significantly reduced by the particles, showing an improved activity co-delivering both drugs using such a drug-delivery system for specific inhibition of TNF-α in the lungs.


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