Delivery of Natural Agents by Means of Mesoporous Silica Nanospheres as a Promising Anticancer Strategy

Natural prodrugs derived from different natural origins (e.g., medicinal plants, microbes, animals) have a long history in traditional medicine. They exhibit a broad range of pharmacological activities, including anticancer effects in vitro and in vivo. They have potential as safe, cost-effective treatments with few side effects, but are lacking in solubility, bioavailability, specific targeting and have short half-lives. These are barriers to clinical application. Nanomedicine has the potential to offer solutions to circumvent these limitations and allow the use of natural pro-drugs in cancer therapy. Mesoporous silica nanoparticles (MSNs) of various morphology have attracted considerable attention in the search for targeted drug delivery systems. MSNs are characterized by chemical stability, easy synthesis and functionalization, large surface area, tunable pore sizes and volumes, good biocompatibility, controlled drug release under different conditions, and high drug-loading capacity, enabling multifunctional purposes. In vivo pre-clinical evaluations, a significant majority of results indicate the safety profile of MSNs if they are synthesized in an optimized way. Here, we present an overview of synthesis methods, possible surface functionalization, cellular uptake, biodistribution, toxicity, loading strategies, delivery designs with controlled release, and cancer targeting and discuss the future of anticancer nanotechnology-based natural prodrug delivery systems.

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Investigation of in vitro permeability and in vivo pharmacokinetic behavior of bare and functionalized MCM-41 and MCM-48 mesoporous silica nanoparticles: a burst and controlled drug release system for raloxifene

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2019.1569028 ◽

2019 ◽

Vol 45 (4) ◽

pp. 587-602 ◽

Cited By ~ 3

Author(s):

Priya Shah ◽

Sadhana J. Rajput

Keyword(s):

Drug Release ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Controlled Drug Release ◽

Release System ◽

Mcm 41 ◽

Pharmacokinetic Behavior

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Functionalized Mesoporous Silica Nanoparticles as Delivery Systems for Doxorubicin: Drug Loading and Release

Applied Sciences ◽

10.3390/app11136121 ◽

2021 ◽

Vol 11 (13) ◽

pp. 6121

Author(s):

Candace M. Day ◽

Martin J. Sweetman ◽

Yunmei Song ◽

Sally E. Plush ◽

Sanjay Garg

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Release Kinetics ◽

Drug Loading ◽

In Vitro Release ◽

Delivery Systems ◽

Stimuli Responsive ◽

Kinetics Of

Functionalized nanoparticles have played a major role in the field of targeted therapy, owing to their ability to control the release and for the selective delivery of entrapped materials to tumours. In this work, we described the loading capacity and in vitro release kinetics of mesoporous silica nanoparticles (MSNs), functionalized with Poly-L-Histidine and Tamoxifen. The model drug Doxorubicin (DOX) was successfully encapsulated into MSN-based systems, using the technique of solvent immersion. A post-surface grafting loading method was investigated on functionalized systems, with DOX loading content determined using HPLC. Dialysis bag diffusion was employed to investigate the release kinetics of DOX-loaded-systems at pH 7.4 and 5. The amount of DOX released from native MSNs systems over a 72 h period at pH 5 was approximately 40%; and at pH 7.4 ≈ 30%. A moderate pH dependent release behaviour was observed with both our functionalized systems: DOX@MSN-PLH and DOX@MSN-PLH-TAM; with approximately 5% of DOX released from DOX@MSN-PLH-TAM at pH 7.4 and about 9% released at pH 7.4 over 72 h. The maximal cumulated release of DOX molecules from DOX@MSN-PLH after 72 h was ≈ 18% at pH 7.4 and ≈ 23% at pH 5, respectively. The outcome of this work offers a promising contribution towards building future stimuli-responsive nano-drug delivery systems.

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pH-Responsive and Biodegradable ZnO-Capped Mesoporous Silica Composite Nanoparticles for Drug Delivery

Materials ◽

10.3390/ma13183950 ◽

2020 ◽

Vol 13 (18) ◽

pp. 3950

Author(s):

Minmin Chen ◽

Jinxia Hu ◽

Cancan Bian ◽

Chenghao Zhu ◽

Chen Chen ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Mesoporous Silica ◽

Mesoporous Silica Nanoparticles ◽

Controlled Drug Release ◽

Composite Nanoparticles ◽

Ph Responsive ◽

Silica Composite

As a drug delivery system (DDS), traditional mesoporous silica nanoparticles (MSNs) suffer from bioaccumulation in vivo and premature drug release in systemic circulation due to low degradation rate and lack of protective gatekeeper. Herein, we developed a safe and intelligent DDS with characteristics of pH-responsive biodegradation and controlled drug release based on mesoporous silica composite nanoparticles (MSCNs) capped with ZnO quantum dots (ZnO QDs). Acidic degradable MSCNs were successfully synthesized by doping Ca2+ and PO43− into the MSNs’ framework. The in vitro doxorubicin hydrochloride (DOX) release was inhibited at neutral pH 7.4 but triggered significantly at pH 5.0 due to the dissociation of ZnO caps. The internalization behavior and cytotoxicity of 4T1 cells indicated MSCNs-ZnO could efficiently deliver DOX into the cells with significant antitumor activity. Such a DDS with pH-responsive biodegradation and controlled drug release has promising potential for cancer therapy.

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Mesoporous Silica Nanoparticles and Mesoporous Bioactive Glasses for Wound Management: From Skin Regeneration to Cancer Therapy

Materials ◽

10.3390/ma14123337 ◽

2021 ◽

Vol 14 (12) ◽

pp. 3337

Author(s):

Sara Hooshmand ◽

Sahar Mollazadeh ◽

Negar Akrami ◽

Mehrnoosh Ghanad ◽

Ahmed El-Fiqi ◽

...

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Skin Regeneration ◽

Bioactive Molecules ◽

Wound Management ◽

Bioactive Glasses ◽

Wide Range

Exploring new therapies for managing skin wounds is under progress and, in this regard, mesoporous silica nanoparticles (MSNs) and mesoporous bioactive glasses (MBGs) offer great opportunities in treating acute, chronic, and malignant wounds. In general, therapeutic effectiveness of both MSNs and MBGs in different formulations (fine powder, fibers, composites etc.) has been proved over all the four stages of normal wound healing including hemostasis, inflammation, proliferation, and remodeling. The main merits of these porous substances can be summarized as their excellent biocompatibility and the ability of loading and delivering a wide range of both hydrophobic and hydrophilic bioactive molecules and chemicals. In addition, doping with inorganic elements (e.g., Cu, Ga, and Ta) into MSNs and MBGs structure is a feasible and practical approach to prepare customized materials for improved skin regeneration. Nowadays, MSNs and MBGs could be utilized in the concept of targeted therapy of skin malignancies (e.g., melanoma) by grafting of specific ligands. Since potential effects of various parameters including the chemical composition, particle size/morphology, textural properties, and surface chemistry should be comprehensively determined via cellular in vitro and in vivo assays, it seems still too early to draw a conclusion on ultimate efficacy of MSNs and MBGs in skin regeneration. In this regard, there are some concerns over the final fate of MSNs and MBGs in the wound site plus optimal dosages for achieving the best outcomes that deserve careful investigation in the future.

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Antimicrobial and antibiofilm activities of meropenem loaded-mesoporous silica nanoparticles against carbapenem-resistant Pseudomonas aeruginosa

Journal of Biomaterials Applications ◽

10.1177/08853282211003848 ◽

2021 ◽

pp. 088532822110038

Author(s):

Mohammad Yousef Memar ◽

Mina Yekani ◽

Hadi Ghanbari ◽

Edris Nabizadeh ◽

Sepideh Zununi Vahed ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Carbapenem Resistant ◽

Toxicity In Vitro ◽

Different Levels

The aims of the present study were the determination of antimicrobial and antibiofilm effects of meropenem-loaded mesoporous silica nanoparticles (MSNs) on carbapenem resistant Pseudomonas aeruginosa ( P. aeruginosa) and cytotoxicity properties in vitro. The meropenem-loaded MSNs had shown antibacterial and biofilm inhibitory activities on all isolates at different levels lower than MICs and BICs of meropenem. The viability of HC-04 cells treated with serial concentrations as MICs and BICs of meropenem-loaded MSNs was 92–100%. According to the obtained results, meropenem-loaded MSNs display the significant antibacterial and antibiofilm effects against carbapenem resistant and biofilm forming P. aeruginosa and low cell toxicity in vitro. Then, the prepared system can be an appropriate option for the delivery of carbapenem for further evaluation in vivo assays.

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Polymeric Mesoporous Silica Nanoparticles for Enhanced Delivery of 5-Fluorouracil In Vitro

Pharmaceutics ◽

10.3390/pharmaceutics11060288 ◽

2019 ◽

Vol 11 (6) ◽

pp. 288 ◽

Cited By ~ 19

Author(s):

Thashini Moodley ◽

Moganavelli Singh

Keyword(s):

Side Effects ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Therapeutic Potential ◽

Mesoporous Silica Nanoparticles ◽

Drug Loading ◽

Hek293 Cells ◽

Cancer Drug ◽

Delivery Vehicles

There is a need for the improvement of conventional cancer treatment strategies by incorporation of targeted and non-invasive procedures aimed to reduce side-effects, drug resistance, and recurrent metastases. The anti-cancer drug, 5-fluorouracil (5-FU), is linked to a variety of induced-systemic toxicities due to its lack of specificity and potent administration regimens, necessitating the development of delivery vehicles that can enhance its therapeutic potential, while minimizing associated side-effects. Polymeric mesoporous silica nanoparticles (MSNs) have gained popularity as delivery vehicles due to their high loading capacities, biocompatibility, and good pharmacokinetics. MSNs produced in this study were functionalized with the biocompatible polymers, chitosan, and poly(ethylene)glycol to produce monodisperse NPs of 36–65 nm, with a large surface area of 710.36 m2/g, large pore volume, diameter spanning 9.8 nm, and a favorable zeta potential allowing for stability and enhanced uptake of 5-FU. Significant drug loading (0.15–0.18 mg5FU/mgmsn), controlled release profiles (15–65%) over 72 hours, and cell specific cytotoxicity in cancer cells (Caco-2, MCF-7, and HeLa) with reduced cell viability (≥50%) over the non-cancer (HEK293) cells were established. Overall, these 5FU-MSN formulations have been shown to be safe and effective delivery systems in vitro, with potential for in vivo applications.

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pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers

Pharmaceutics ◽

10.3390/pharmaceutics13040460 ◽

2021 ◽

Vol 13 (4) ◽

pp. 460

Author(s):

Minja Mladenović ◽

Ibrahim Morgan ◽

Nebojša Ilić ◽

Mohamad Saoud ◽

Marija V. Pergal ◽

...

Keyword(s):

Drug Delivery ◽

Mesoporous Silica ◽

Inductively Coupled Plasma ◽

Drug Delivery Systems ◽

Mesoporous Silica Nanoparticles ◽

Release Kinetics ◽

Delivery Systems ◽

Emission Spectrometry ◽

Ph Responsive

Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer.

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Organosilane and Polyethylene Glycol Functionalized Magnetic Mesoporous Silica Nanoparticles as Carriers for CpG Immunotherapy In Vitro and In Vivo

PLoS ONE ◽

10.1371/journal.pone.0140265 ◽

2015 ◽

Vol 10 (10) ◽

pp. e0140265 ◽

Cited By ~ 10

Author(s):

Hengrui Zheng ◽

Songsong Wen ◽

Yang Zhang ◽

Zhenliang Sun

Keyword(s):

Polyethylene Glycol ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Magnetic Mesoporous Silica

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Stealth doxorubicin conjugated bimetallic selenium/silver nanoparticles for targeted cervical cancer therapy

Advances in Natural Sciences Nanoscience and Nanotechnology ◽

10.1088/2043-6262/ac389c ◽

2021 ◽

Vol 12 (4) ◽

pp. 045006

Author(s):

Thoko Malinga ◽

Tukayi Kudanga ◽

Londiwe Simphiwe Mbatha

Keyword(s):

Cervical Cancer ◽

Folic Acid ◽

Colloidal Stability ◽

Controlled Drug Release ◽

Delivery Systems ◽

Drug Binding ◽

Cervical Cancer Cells ◽

Diphenyl Tetrazolium Bromide

Abstract Bimetallic nanosized delivery systems are attracting a lot of research interest as alternatives to monometallic delivery systems. This study evaluated the ability of bimetallic selenium silver chitosan pegylated folic acid targeted nanoparticles (SeAgChPEGFA NPs) to deliver doxorubicin (DOX) in cervical cancer cells. Comparison studies using monometallic selenium chitosan pegylated folic acid (SeChPEGFA NPs) targeted NPs and free DOX were also conducted. The prepared NPs and their drug nanocomplexes were characterised morphologically and physico-chemically. Drug binding and releasing studies were conducted under a simulated environment in vitro. The cytotoxicity and apoptosis studies were studied using the 3-[(4, 5-dimethylthiazol-2-yl)−2, 5-diphenyl tetrazolium bromide] (MTT) assay and the dual dye staining. The findings revealed that the bimetallic SeAgChPEGFA NPs displayed better colloidal stability, superior physico-chemical qualities, and higher binding abilities in comparison with monometallic SeChPEGFA NPs. In addition, the SeAgChPEGFA NPs showed the pH-triggered controlled drug release and cell-specific cytotoxicity. These findings suggest that the bimetallic NPs are superior delivery systems when compared to their monometallic NPs and free drug counterparts, thus, setting a platform for further in vivo examination.

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