The Architecture and Function of Monoclonal Antibody‐Functionalized Mesoporous Silica Nanoparticles Loaded with Mifepristone: Repurposing Abortifacient for Cancer Metastatic Chemoprevention

Gao, Yu; Gu, Songen; Zhang, Yingying; Xie, Xiaodong; Yu, Ting; Lu, Yusheng; Zhu, Yewei; Chen, Wenge; Zhang, Huijuan; Dong, Haiyan; Sinko, Patrick J.; Jia, Lee

doi:10.1002/smll.201600550

Cited by 48 publications

(44 citation statements)

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“…However, MCNs could inhibit cell growth in a dose-dependant manner. In this experiment, we found that MIF had no effect at low concentration, and was apt to precipitate at high concentration because of its strong hydrophobicity leading to decreased activity, which was consistent with our previous report [33]. Compared with free MIF, MCNs showed enhanced anti-proliferative activity, indicating that the anticancer effects of MCNs could be due to the synergistic effects of Cs and MIF.…”

Section: Resultssupporting

confidence: 91%

“…Besides, the sustained release of MIF from the CNs could be another reason for the enhanced anti-proliferative efficiency of MCN. In our previous report, we loaded MIF into mesoporous silica nanoparticles (MSNs) coated with aEpCAM (aE-MSN-M) to target circulating tumor cells for cancer metastasis prevention, and also found that MIF entrapped in aE-MSN-M increased its efficacy by sustained release to reduce drug crystallization [33]. These results suggested that MCNs might be a good drug delivery system for delivery of MIF for cancer therapy.…”

Section: Resultsmentioning

confidence: 98%

“…6). This is because MIF, with weakly basic nitrogen, is more likely to dissolve in acidic solution [33]. The sustained-release manner of MCNs could prolong the time of drug absorption in the gastrointestinal tract, which might be beneficial to enhanced bioavailability of MIF [31,34].…”

Section: Resultsmentioning

confidence: 99%

“…The supernatant was collected after centrifugation and the concentration of MIF was analyzed with a Waters-2695 HPLC system equipped with a 2487 UV detector. MIF was separated on an Inertstil ODS2 C18 (150 × 4.6 mm, 5 μm) column with the mobile phase of acetonitrile–water (80:20 v/v), injection volume of 20 μL, flow rate of 1.0 mL/min, ambient column temperature and detection wavelength of 302 nm [33]. …”

Section: Methodsmentioning

confidence: 99%

“…The in vitro release of MIF from the MCNs was performed using the dialysis bag diffusion technique [33]. The dialysis bag was cut into small pieces of appropriate length and boiled for 10 min in a volume (500 mL) of 2% (w/v) sodium bicarbonate and 1 mmol/L EDTA-2Na (pH 8.0) before use.…”

Section: Methodsmentioning

confidence: 99%

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Chitosan-based nanoparticles for improved anticancer efficacy and bioavailability of mifepristone

Zhang¹,

Wu²,

Li³

et al. 2016

Beilstein J. Nanotechnol.

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In addition to its well-known abortifacient effect, mifepristone (MIF) has been used as an anticancer drug for various cancers in many studies with an in-depth understanding of the mechanism of action. However, application of MIF is limited by its poor water solubility and low oral bioavailability. In this work, we developed a drug delivery system based on chitosan nanoparticles (CNs) to improve its bioavailability and anticancer activity. The MIF-loaded chitosan nanoparticles (MCNs) were prepared by convenient ionic gelation techniques between chitosan (Cs) and tripolyphosphate (TPP). The preparation conditions, including Cs concentration, TPP concentration, Cs/MIF mass ratio, and pH value of the TPP solution, were optimized to gain better encapsulation efficiency (EE) and drug loading capacity (DL). MCNs prepared with the optimum conditions resulted in spherical particles with an average size of 200 nm. FTIR and XRD spectra verified that MIF was successfully encapsulated in CNs. The EE and DL of MCNs determined by HPLC were 86.6% and 43.3%, respectively. The in vitro release kinetics demonstrated that MIF was released from CNs in a sustained-release manner. Compared with free MIF, MCNs demonstrated increased anticancer activity in several cancer cell lines. Pharmacokinetic studies in male rats that were orally administered MCNs showed a 3.2-fold increase in the area under the curve from 0 to 24 h compared with free MIF. These results demonstrated that MCNs could be developed as a potential delivery system for MIF to improve its anticancer activity and bioavailability.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Chitosan-based nanoparticles for improved anticancer efficacy and bioavailability of mifepristone

Zhang¹,

Wu²,

Li³

et al. 2016

Beilstein J. Nanotechnol.

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Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms

et al. 2023

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ImportanceAdenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for adenomyosis treatment.ObjectiveTo determine whether mifepristone is effective and safe for adenomyosis treatment.Design, Setting, and ParticipantsThis multicenter, placebo-controlled, double-blind randomized clinical trial was conducted in 10 hospitals in China. In total, 134 patients with adenomyosis pain symptoms were enrolled. Trial enrollment began in May 2018 and was completed in April 2019, and analyses were conducted from October 2019 to February 2020.InterventionsParticipants were randomized 1:1 to receive mifepristone 10 mg or placebo orally once a day for 12 weeks.Main Outcomes and MeasuresThe primary end point was the change in adenomyosis-associated dysmenorrhea intensity, evaluated by the visual analog scale (VAS) after 12 weeks of treatment. Secondary end points included the change in menstrual blood loss, increased level of hemoglobin in patients with anemia, CA125 level, platelet count, and uterine volume after 12 weeks of treatment. Safety was assessed according to adverse events, vital signs, gynecological examinations, and laboratory evaluations.ResultsIn total, 134 patients with adenomyosis and dysmenorrhea were randomly assigned, and 126 patients were included in the efficacy analysis, including 61 patients (mean [SD] age, 40.2 [4.6] years) randomized to receive mifepristone and 65 patients (mean [SD] age, 41.7 [5.0] years) randomized to received the placebo. The characteristics of the included patients at baseline were similar between groups. The mean (SD) change in VAS score was −6.63 (1.92) in the mifepristone group and −0.95 (1.75) in the placebo group (P &lt; .001). The total remission rates for dysmenorrhea in the mifepristone group were significantly better than those in the placebo group (effective remission: 56 patients [91.8%] vs 15 patients [23.1%]; complete remission: 54 patients [88.5%] vs 4 patients [6.2%]). All the secondary end points showed significant improvements after mifepristone treatment for menstrual blood loss, hemoglobin (mean [SD] change from baseline: 2.13 [1.38] g/dL vs 0.48 [0.97] g/dL; P &lt; .001), CA125 (mean [SD] change from baseline: −62.23 [76.99] U/mL vs 26.89 [118.70] U/mL; P &lt; .001), platelet count (mean [SD] change from baseline: −28.87 [54.30]×103/µL vs 2.06 [41.78]×103/µL; P &lt; .001), and uterine volume (mean [SD] change from baseline: −29.32 [39.34] cm3 vs 18.39 [66.46] cm3; P &lt; .001). Safety analysis revealed no significant difference between groups, and no serious adverse events were reported.Conclusions and RelevanceThis randomized clinical trial showed that mifepristone could be a new option for treating patients with adenomyosis, based on its efficacy and acceptable tolerability.Trial RegistrationClinicalTrials.gov Identifier: NCT03520439

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Sol–Gel‐Based Advanced Porous Silica Materials for Biomedical Applications

Lei

Guo

Noureddine

et al. 2020

Adv Funct Materials

166

109

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Porous silica-based materials have burgeoning applications ranging from fillers and additives, to adsorbents, catalysts, and recently therapeutic agents and vaccines in nanomedicine. The preponderance of these materials is made by sol-gel processing wherein soluble silica precursors are reacted to form amorphous networks composed of siloxane bonds. The facile sol-gel approach allows for an unlimited variety of binary tertiary and more complex chemical compositions including organic ligands and networks resulting in so-called organic-inorganic hybrid materials. Here, a brief review of the recent progress in sol-gel-derived silica materials prepared as particles, thin films, biosilica/silica bioreplicas (of molecules, cells and organisms), and their related preparation, properties, and bioapplications is provided. First, it highlights the recent achievements of mesoporous silica nanoparticles in biomedical applications, including therapeutic agent delivery, multimodal imaging and theranostics, and bone tissue engineering and repair. Second, the research in evaporation-induced self-assembly (EISA)-based mesostructured silica thin films and cell-directed EISA in bio/nano interfaces for various bioapplications, such as bioactive coatings, biosensing, and living cell immobilization, has been reviewed. Third, the pioneering work in biomimetic silicification/ immobilization of biomolecules and bio-organisms and silica bioreplication of complex bio-organisms is summarized. Finally, it is concluded with personal perspectives on the directions of future work on this field. In 1846, Ebelmen synthesized tetraethylorthosilicate (TEOS) from SiCl 4 and ethanol and exposed it to water forming a transparent glassy material upon gelation and drying (now recognized to be a microporous xerogel). In 1864, the term "sol-gel" was first proposed by Graham during his work on silica sols. [2] In 1912-1915, Patrick developed an economically viable and rapid sol-gel process to mass-produce silica gel from sodium silicate (Na 2 SiO 3). And in 1931, Kistler reported the first synthesis of a highly porous silica (SiO 2) form, termed as "aerogel," which was a porous ultralight material derived from hydrolytic polycondensation of silicic acid (Si(OH) 4) to form a gel followed by supercritical drying to avoid drying shrinkage. [3] All of these efforts can be regarded as the beginning of modern sol-gel based silica materials, which are now ripening for wide range of applications, including the two pillars of the chemistry practice (synthesis and analysis), protective coatings, adsorption, chromatography, separation, biotechnology, energy conservation, cultural heritage restoration, and environmental remediation as well as many other fields of contemporary technology. [4] Based on the breakthroughs in synthesis, the recent two decades have witnessed an exponential increase in research of sol-gel-based silica materials for biomedical applications. Silica is inherently compatible with biological systems and was accepted as "Generally Recognized As Saf...

show abstract

The Architecture and Function of Monoclonal Antibody‐Functionalized Mesoporous Silica Nanoparticles Loaded with Mifepristone: Repurposing Abortifacient for Cancer Metastatic Chemoprevention

Cited by 48 publications

References 50 publications

Chitosan-based nanoparticles for improved anticancer efficacy and bioavailability of mifepristone

Chitosan-based nanoparticles for improved anticancer efficacy and bioavailability of mifepristone

Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms

Sol–Gel‐Based Advanced Porous Silica Materials for Biomedical Applications

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