Pentapeptide-decorated silica nanoparticles loading salmon calcitonin for in vivo osteoporosis treatment with sustained hypocalcemic effect

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

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Current Stimuli-Responsive Mesoporous Silica Nanoparticles for Cancer Therapy

Pharmaceutics ◽

10.3390/pharmaceutics13010071 ◽

2021 ◽

Vol 13 (1) ◽

pp. 71

Author(s):

Thashini Moodley ◽

Moganavelli Singh

Keyword(s):

Cancer Therapy ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Therapeutic Agents ◽

Metal Species ◽

Stimuli Responsive ◽

Combination Drug ◽

Incidence And Mortality

With increasing incidence and mortality rates, cancer remains one of the most devastating global non-communicable diseases. Restricted dosages and decreased bioavailability, often results in lower therapeutic outcomes, triggering the development of resistance to conventionally used drug/gene therapeutics. The development of novel therapeutic strategies using multimodal nanotechnology to enhance specificity, increase bioavailability and biostability of therapeutics with favorable outcomes is critical. Gated vectors that respond to endogenous or exogenous stimuli, and promote targeted tumor delivery without prematurely cargo loss are ideal. Mesoporous silica nanoparticles (MSNs) are effective delivery systems for a variety of therapeutic agents in cancer therapy. MSNs possess a rigid framework and large surface area that can incorporate supramolecular constructs and varying metal species that allow for stimuli-responsive controlled release functions. Its high interior loading capacity can incorporate combination drug/gene therapeutic agents, conferring increased bioavailability and biostability of the therapeutic cargo. Significant advances in the engineering of MSNs structural and physiochemical characteristics have since seen the development of nanodevices with promising in vivo potential. In this review, current trends of multimodal MSNs being developed and their use in stimuli-responsive passive and active targeting in cancer therapy will be discussed, focusing on light, redox, pH, and temperature stimuli.

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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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Formulation development and in vitro–in vivo assessment of protransfersomal gel of anti-resorptive drug in osteoporosis treatment

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2021.121060 ◽

2021 ◽

pp. 121060

Author(s):

Suman Gyanewali ◽

Prashant Kesharwani ◽

Afsana ◽

Farhan Jalees Ahmad ◽

Ritu Trivedi ◽

...

Keyword(s):

Osteoporosis Treatment ◽

Formulation Development ◽

In Vivo Assessment

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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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Evaluation of the Skin Sensitization Potential of Silica nanoparticles using in vitro and in vivo assay

Toxicology Letters ◽

10.1016/s0378-4274(21)00415-x ◽

2021 ◽

Vol 350 ◽

pp. S72

Author(s):

D.H. Lee ◽

S.-H. Kim ◽

J.H. Lee ◽

J.-Y Yang ◽

H.-S. Shin ◽

...

Keyword(s):

Silica Nanoparticles ◽

Skin Sensitization ◽

In Vivo Assay

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The Bromodomain Inhibitor N-Methyl pyrrolidone Prevents Osteoporosis and BMP-Triggered Sclerostin Expression in Osteocytes

International Journal of Molecular Sciences ◽

10.3390/ijms19113332 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3332 ◽

Cited By ~ 1

Author(s):

Barbara Siegenthaler ◽

Chafik Ghayor ◽

Bebeka Gjoksi-Cosandey ◽

Nisarat Ruangsawasdi ◽

Franz Weber

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Osteoporosis Treatment ◽

Estrogen Deficiency ◽

Bone Morphogenetic Protein 2 ◽

Protein Levels ◽

Osteoporosis Management ◽

Promising Target

(1) Background: In an adult skeleton, bone is constantly renewed in a cycle of bone resorption, followed by bone formation. This coupling process, called bone remodeling, adjusts the quality and quantity of bone to the local needs. It is generally accepted that osteoporosis develops when bone resorption surpasses bone formation. Osteoclasts and osteoblasts, bone resorbing and bone forming cells respectively, are the major target in osteoporosis treatment. Inside bone and forming a complex network, the third and most abundant cells, the osteocytes, have long remained a mystery. Osteocytes are responsible for mechano-sensation and -transduction. Increased expression of the osteocyte-derived bone inhibitor sclerostin has been linked to estrogen deficiency-induced osteoporosis and is therefore a promising target for osteoporosis management. (2) Methods: Recently we showed in vitro and in vivo that NMP (N-Methyl-2-pyrrolidone) is a bioactive drug enhancing the BMP-2 (Bone Morphogenetic Protein 2) induced effect on bone formation while blocking bone resorption. Here we tested the effect of NMP on the expression of osteocyte-derived sclerostin. (3) Results: We found that NMP significantly decreased sclerostin mRNA and protein levels. In an animal model of osteoporosis, NMP prevented the estrogen deficiency-induced increased expression of sclerostin. (4) Conclusions: These results support the potential of NMP as a novel therapeutic compound for osteoporosis management, since it preserves bone by a direct interference with osteoblasts and osteoclasts and an indirect one via a decrease in sclerostin expression by osteocytes.

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