8 results on '"mesoporous silica nanoparticle"'
Search Results
2. Redox-Triggered Release of Moxifloxacin from Mesoporous Silica Nanoparticles Functionalized with Disulfide Snap-Tops Enhances Efficacy Against Pneumonic Tularemia in Mice.
- Author
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Lee, Bai-Yu, Li, Zilu, Clemens, Daniel L, Dillon, Barbara Jane, Hwang, Angela A, Zink, Jeffrey I, and Horwitz, Marcus A
- Subjects
Animals ,Mice ,Inbred BALB C ,Mice ,Tularemia ,Silicon Dioxide ,Fluoroquinolones ,Drug Delivery Systems ,Female ,Nanoparticles ,Moxifloxacin ,disulfide snap-top ,francisella tularensis ,intracellular delivery ,mesoporous silica nanoparticle ,redox potential ,Rare Diseases ,Biodefense ,Biotechnology ,Nanotechnology ,Bioengineering ,Prevention ,Emerging Infectious Diseases ,Orphan Drug ,Vector-Borne Diseases ,Vaccine Related ,Infectious Diseases ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Infection ,Nanoscience & Nanotechnology - Abstract
Effective and rapid treatment of tularemia is needed to reduce morbidity and mortality of this potentially fatal infectious disease. The etiologic agent, Francisella tularensis, is a facultative intracellular bacterial pathogen which infects and multiplies to high numbers in macrophages. Nanotherapeutics are particularly promising for treatment of infectious diseases caused by intracellular pathogens, whose primary host cells are macrophages, because nanoparticles preferentially target and are avidly internalized by macrophages. A mesoporous silica nanoparticle (MSN) has been developed functionalized with disulfide snap-tops that has high drug loading and selectively releases drug intracellularly in response to the redox potential. These nanoparticles, when loaded with Hoechst fluorescent dye, release their cargo exclusively intracellularly and stain the nuclei of macrophages. The MSNs loaded with moxifloxacin kill F. tularensis in macrophages in a dose-dependent fashion. In a mouse model of lethal pneumonic tularemia, MSNs loaded with moxifloxacin prevent weight loss, illness, and death, markedly reduce the burden of F. tularensis in the lung, liver, and spleen, and are significantly more efficacious than an equivalent amount of free drug. An important proof-of-principle for the potential therapeutic use of a novel nanoparticle drug delivery platform for the treatment of infectious diseases is provided.
- Published
- 2016
3. Irinotecan Delivery by Lipid-Coated Mesoporous Silica Nanoparticles Shows Improved Efficacy and Safety over Liposomes for Pancreatic Cancer
- Author
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Liu, Xiangsheng, Situ, Allen, Kang, Yanan, Villabroza, Katie Rose, Liao, Yupei, Chang, Chong Hyun, Donahue, Timothy, Nel, Andre E, and Meng, Huan
- Subjects
Digestive Diseases ,Pancreatic Cancer ,Orphan Drug ,Bioengineering ,Rare Diseases ,Cancer ,Nanotechnology ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Adenocarcinoma ,Animals ,Antineoplastic Agents ,Phytogenic ,Camptothecin ,Cell Line ,Tumor ,Drug Liberation ,Female ,Irinotecan ,Lipid Bilayers ,Liposomes ,Mice ,Nanoparticles ,Pancreatic Neoplasms ,Silicon Dioxide ,irinotecan ,FOLFIRINOX ,proton gradient ,lipid bilayer ,mesoporous silica nanoparticle ,pancreatic cancer ,toxicity reduction ,Nanoscience & Nanotechnology - Abstract
Urgent intervention is required to improve the 5 year survival rate of pancreatic ductal adenocarcinoma (PDAC). While the four-drug regimen, FOLFIRINOX (comprising irinotecan, 5-fluorouracil, oxaliplatin, and leucovorin), has a better survival outcome than the more frequently used gemcitabine, the former treatment platform is highly toxic and restricted for use in patients with good performance status. Since irinotecan contributes significantly to FOLFIRINOX toxicity (bone marrow and gastrointestinal tract), our aim was to reduce the toxicity of this drug by a custom-designed mesoporous silica nanoparticle (MSNP) platform, which uses a proton gradient for high-dose irinotecan loading across a coated lipid bilayer (LB). The improved stability of the LB-coated MSNP (LB-MSNP) carrier allowed less drug leakage systemically with increased drug concentrations at the tumor sites of an orthotopic Kras-derived PDAC model compared to liposomes. The LB-MSNP nanocarrier was also more efficient for treating tumor metastases. Equally important, the reduced leakage and slower rate of drug release by the LB-MSNP carrier dramatically reduced the rate of bone marrow, gastrointestinal, and liver toxicity compared to the liposomal carrier. We propose that the combination of high efficacy and reduced toxicity by the LB-MSNP carrier could facilitate the use of irinotecan as a first-line therapeutic to improve PDAC survival.
- Published
- 2016
4. Mesoporous Silica Nanoparticles with pH-Sensitive Nanovalves for Delivery of Moxifloxacin Provide Improved Treatment of Lethal Pneumonic Tularemia
- Author
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Li, Zilu, Clemens, Daniel L, Lee, Bai-Yu, Dillon, Barbara Jane, Horwitz, Marcus A, and Zink, Jeffrey I
- Subjects
Biodefense ,Infectious Diseases ,Nanotechnology ,Bioengineering ,Prevention ,Emerging Infectious Diseases ,Vaccine Related ,Rare Diseases ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Animals ,Benzimidazoles ,Drug Delivery Systems ,Fluoroquinolones ,Francisella tularensis ,Humans ,Hydrogen-Ion Concentration ,Macrophages ,Mice ,Microbial Viability ,Moxifloxacin ,Nanoparticles ,Phosphorous Acids ,Pneumonia ,Porosity ,Silicon Dioxide ,Treatment Outcome ,Tularemia ,mesoporous silica nanoparticle ,optimization of uptake and release capacities ,pH-sensitive nanovalve ,intracellular bacteria ,tularemia ,efficacy ,Nanoscience & Nanotechnology - Abstract
We have optimized mesoporous silica nanoparticles (MSNs) functionalized with pH-sensitive nanovalves for the delivery of the broad spectrum fluoroquinolone moxifloxacin (MXF) and demonstrated its efficacy in treating Francisella tularensis infections both in vitro and in vivo. We compared two different nanovalve systems, positive and negative charge modifications of the mesopores, and different loading conditions-varying pH, cargo concentration, and duration of loading-and identified conditions that maximize both the uptake and release capacity of MXF by MSNs. We have demonstrated in macrophage cell culture that the MSN-MXF delivery platform is highly effective in killing F. tularensis in infected macrophages, and in a mouse model of lethal pneumonic tularemia, we have shown that the drug-loaded MSNs are much more effective in killing F. tularensis than an equivalent amount of free MXF.
- Published
- 2015
5. Use of a Lipid-Coated Mesoporous Silica Nanoparticle Platform for Synergistic Gemcitabine and Paclitaxel Delivery to Human Pancreatic Cancer in Mice
- Author
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Meng, Huan, Wang, Meiying, Liu, Huiyu, Liu, Xiangsheng, Situ, Allen, Wu, Bobby, Ji, Zhaoxia, Chang, Chong Hyun, and Nel, Andre E
- Subjects
Cancer ,Orphan Drug ,Rare Diseases ,Digestive Diseases ,Nanotechnology ,Bioengineering ,Pancreatic Cancer ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Albumins ,Animals ,Antineoplastic Agents ,Cell Line ,Tumor ,Cell Transformation ,Neoplastic ,Cytidine Deaminase ,Deoxycytidine ,Drug Carriers ,Drug Synergism ,Female ,Gene Expression Regulation ,Neoplastic ,Humans ,Lipid Bilayers ,Mice ,Nanoparticles ,Paclitaxel ,Pancreatic Neoplasms ,Porosity ,Silicon Dioxide ,Gemcitabine ,gemcitabine ,paclitaxel ,co-delivery ,synergy ,ratiometric ,mesoporous silica nanoparticle ,pancreatic cancer ,Nanoscience & Nanotechnology - Abstract
Recently, a commercial albumin-bound paclitaxel (PTX) nanocarrier (Abraxane) was approved as the first new drug for pancreatic ductal adenocarcinoma in almost a decade. PTX improves the pharmaceutical efficacy of the first-line pancreatic cancer drug, gemcitabine (GEM), through suppression of the tumor stroma and inhibiting the expression of the GEM-inactivating enzyme, cytidine deaminase (CDA). We asked, therefore, whether it was possible to develop a mesoporous silica nanoparticle (MSNP) carrier for pancreatic cancer to co-deliver a synergistic GEM/PTX combination. High drug loading was achieved by a custom-designed coated lipid film technique to encapsulate a calculated dose of GEM (40 wt %) by using a supported lipid bilayer (LB). The uniform coating of the 65 nm nanoparticles by a lipid membrane allowed incorporation of a sublethal amount of hydrophobic PTX, which could be co-delivered with GEM in pancreatic cells and tumors. We demonstrate that ratiometric PTX incorporation and delivery by our LB-MSNP could suppress CDA expression, contemporaneous with induction of oxidative stress as the operating principle for PTX synergy. To demonstrate the in vivo efficacy, mice carrying subcutaneous PANC-1 xenografts received intravenous (IV) injection of PTX/GEM-loaded LB-MSNP. Drug co-delivery provided more effective tumor shrinkage than GEM-loaded LB-MSNP, free GEM, or free GEM plus Abraxane. Comparable tumor shrinkage required coadministration of 12 times the amount of free Abraxane. High-performance liquid chromatography analysis of tumor-associated GEM metabolites confirmed that, compared to free GEM, MSNP co-delivery increased the phosphorylated DNA-interactive GEM metabolite 13-fold and decreased the inactivated and deaminated metabolite 4-fold. IV injection of MSNP-delivered PTX/GEM in a PANC-1 orthotopic model effectively inhibited primary tumor growth and eliminated metastatic foci. The enhanced in vivo efficacy of the dual delivery carrier could be achieved with no evidence of local or systemic toxicity. In summary, we demonstrate the development of an effective LB-MSNP nanocarrier for synergistic PTX/GEM delivery in pancreatic cancer.
- Published
- 2015
6. The Designs, Syntheses and Medical Applications of Mesoporous Silica Nanoparticle Based Drug Delivery Systems
- Author
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Li, Zongxi
- Subjects
Inorganic chemistry ,Nanotechnology ,Medicine ,Cancer Chemotherapy ,Controlled Release ,Drug Delivery ,Mesoporous Silica Nanoparticle ,Nanomedicine - Abstract
The work covered in this thesis focuses on the development of mesoporous silica nanoparticle-based platforms for the controlled delivery of therapeutic agents. The first part of the thesis discusses the physical chemical properties of mesoporous silica nanoparticles, including the studies on their uptake and release capacities and the physical states of the encapsulated cargo molecules using spectroscopic methods. The second part of the thesis describes the organic functionalizations of the mesoporous silica nanoparticles with novel cyclodextrin-based nanogate systems, achieving pH and redox responsive controlled release mechanisms, as well as cargo size selectivity for the release from a dual-loaded system. In the third part of this thesis, several examples of the biomedical applications of the mesoporous silica nanoparticle based drug delivery systems are shown. This includes the in vitro delivery of small interference RNA to shutdown endogenous and exogenous gene expressions in cells using the polyethyleneimine coated nanoparticles, the in vivo delivery of anti-cancer therapeutic to achieve tumor suppression effects on mice models, and the in vivo delivery of anti-microbial therapeutic to achieve animal protection from anthrax lethal toxins. A combination of all these areas of research demonstrate the advancement of the mesoporous silica nanoparticle based drug delivery system towards utilization within living organisms, and realization of medicine on the nanoscale.
- Published
- 2012
7. Irinotecan Delivery by Lipid-Coated Mesoporous Silica Nanoparticles Shows Improved Efficacy and Safety over Liposomes for Pancreatic Cancer
- Author
-
Huan Meng, Timothy R. Donahue, Xiangsheng Liu, Katie Rose Villabroza, Yu-Pei Liao, Andre E. Nel, Allen Situ, Yanan Kang, and Chong Hyun Chang
- Subjects
toxicity reduction ,FOLFIRINOX ,Lipid Bilayers ,pancreatic cancer ,General Physics and Astronomy ,02 engineering and technology ,Pharmacology ,01 natural sciences ,Mice ,Phytogenic ,Nanotechnology ,General Materials Science ,Cancer ,Liposome ,Tumor ,General Engineering ,021001 nanoscience & nanotechnology ,Silicon Dioxide ,5.1 Pharmaceuticals ,Toxicity ,Female ,Development of treatments and therapeutic interventions ,0210 nano-technology ,medicine.drug ,Materials science ,Antineoplastic Agents ,Bioengineering ,Adenocarcinoma ,010402 general chemistry ,Irinotecan ,Article ,Cell Line ,Rare Diseases ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Animals ,Nanoscience & Nanotechnology ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Gemcitabine ,digestive system diseases ,0104 chemical sciences ,Oxaliplatin ,lipid bilayer ,Pancreatic Neoplasms ,Drug Liberation ,Orphan Drug ,Liposomes ,mesoporous silica nanoparticle ,Nanoparticles ,Camptothecin ,Nanocarriers ,Digestive Diseases ,proton gradient - Abstract
Urgent intervention is required to improve the 5 year survival rate of pancreatic ductal adenocarcinoma (PDAC). While the four-drug regimen, FOLFIRINOX (comprising irinotecan, 5-fluorouracil, oxaliplatin, and leucovorin), has a better survival outcome than the more frequently used gemcitabine, the former treatment platform is highly toxic and restricted for use in patients with good performance status. Since irinotecan contributes significantly to FOLFIRINOX toxicity (bone marrow and gastrointestinal tract), our aim was to reduce the toxicity of this drug by a custom-designed mesoporous silica nanoparticle (MSNP) platform, which uses a proton gradient for high-dose irinotecan loading across a coated lipid bilayer (LB). The improved stability of the LB-coated MSNP (LB-MSNP) carrier allowed less drug leakage systemically with increased drug concentrations at the tumor sites of an orthotopic Kras-derived PDAC model compared to liposomes. The LB-MSNP nanocarrier was also more efficient for treating tumor metastases. Equally important, the reduced leakage and slower rate of drug release by the LB-MSNP carrier dramatically reduced the rate of bone marrow, gastrointestinal, and liver toxicity compared to the liposomal carrier. We propose that the combination of high efficacy and reduced toxicity by the LB-MSNP carrier could facilitate the use of irinotecan as a first-line therapeutic to improve PDAC survival.
- Published
- 2016
8. Intracellular Delivery: Redox-Triggered Release of Moxifloxacin from Mesoporous Silica Nanoparticles Functionalized with Disulfide Snap-Tops Enhances Efficacy Against Pneumonic Tularemia in Mice (Small 27/2016).
- Author
-
Lee, Bai-Yu and Lee, Bai-Yu
- Abstract
The drug trapping and intracellular release mechanism of redox-responsive disulfide snap-top mesoporous silica nanoparticles (MSN-SS-MXF) is depicted by J. I. Zink, M. A. Horwitz and co-workers on page 3690. Mesoporous silica nanoparticles with antibiotic (cyan) trapped within their pores by disulfide snap-tops are avidly ingested by macrophages. The intracellular redox potential reduces the disulfide (yellow) in the stalk (green/blue), releases the caps (orange) and frees drug to kill Francisella tularensis (green). Artwork by Bastian Ruehle.
- Published
- 2016
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