STAT6 siRNA Matrix-Loaded Gelatin Nanocarriers: Formulation, Characterization, and<i>Ex Vivo</i>Proof of Concept Using Adenocarcinoma Cells

Youngren, Susanne R.; Tekade, Rakesh K.; Gustilo, Brianne; Hoffmann, Peter; Chougule, Mahavir B.

doi:10.1155/2013/858946

Cited by 71 publications

(23 citation statements)

References 90 publications

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“…31 Additionally, another study reported that PEBP4 inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy. 32 Our finding showed that downregulation of PEBP4 induces EMT and contributes to cisplatin resistance. We further establish miR-15b-PEBP4 as another important pathway regulating EMT and chemoresistance of lung adenocarcinoma cells.…”

Section: Discussionmentioning

confidence: 58%

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miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

et al. 2015

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MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood. We detected miR-15b expression in two lung adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects of miR-15b on the metastasis and the chemosensitivity of cancer cells, using both gain- and loss-of-function studies. The correlation between miR-15b level and chemoresistance was further investigated in clinical lung adenocarcinoma specimens. miR-15b was significantly upregulated in cisplatin-resistant lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-15b regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo. Further studies identified phosphatidylethanolamine-binding protein 4 (PEBP4) as a direct and functional target of miR-15b. Small-interfering RNA-mediated PEBP4 knockdown revealed similar effects as that of ectopic miR-15b expression, whereas overexpression of PEBP4 attenuated the function of miR-15b in lung adenocarcinoma cells. Increased miR-15b expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and was proved to be correlated with low expression of PEBP4, decreased sensitivity to cisplatin and poor prognosis. Our results suggest that upregulation of miR-15b could suppress PEBP4 expression and in turn contribute to chemoresistance of lung adenocarcinoma cells to cisplatin.

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Section: Discussionmentioning

confidence: 58%

“…30,31 In gastric cancer cells, miR-15b promotes cell growth and metastasis both in vitro and in vivo. 32 In addition, it could regulate endothelial differentiation of breast cancer stem-like cells. 33 Moreover, miR-15b plays an important role in mediating drug resistance by targeting multiple drug-resistance-related genes.…”

Section: Discussionmentioning

confidence: 99%

miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

et al. 2015

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“…DTX-CNTs exhibited superior drug release profile especially at acidic pH corresponding to conditions existing at tumorous site. So, carboxylated nanotubes present themselves as potential cargo for anticancer agents and can bring upheaval in the field of cancer therapy but in vivo studies shall be essential to have better insight of their toxicological profile (54)(55)(56)(57). Although, higher hemolytic toxicity of naked CNTs and dendrimer mandates their surface modification by some appropriate strategy (like PEGylation).…”

Section: Resultsmentioning

confidence: 99%

Dendrimer, Liposomes, Carbon Nanotubes and PLGA Nanoparticles: One Platform Assessment of Drug Delivery Potential

Mody¹,

Tekade²,

Mehra³

et al. 2014

AAPS PharmSciTech

117

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Abstract. Liposomes (LIP), nanoparticles (NP), dendrimers (DEN), and carbon nanotubes (CNTs), represent eminent classes of drug delivery devices. A study was carried out herewith by employing docetaxel (DTX) as model drug to assess their comparative drug delivery potentials. Under optimized conditions, highest entrapment of DTX was observed in CNT-based formulation (DTX-CNTs, 74.70± 4.9%) followed by nanoparticles (DTX-NP, 62.34±1.5%), liposome (49.2±1.51%), and dendrimers (28.26± 1.74%). All the formulations were found to be of nanometric size. In vitro release studies were carried out in PBS (pH 7.0 and 4.0), wherein all the formulations showed biphasic release pattern. Cytotoxicity assay in human cervical cancer SiHa cells inferred lowest IC 50 value of 1,235.09±41.93 nM with DTX-CNTs, followed by DTX-DEN, DTX-LIP, DTX-NP with IC 50 values of 1,571.22±151.27, 1,653.98±72.89, 1,922.75±75.15 nM, respectively. Plain DTX showed higher hemolytic toxicity of 22.48±0.94%, however loading of DTX inside nanocarriers drastically reduced its hemolytic toxicity (DTX-DEN, 17.22±0.48%; DTX-LIP, 4.13±0.19%; DTX-NP, 6.43±0.44%; DTX-CNTs, 14.87±1.69%).

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“…The natural polymers that have commonly been used for preparation of polymeric nanoparticles are albumin, chitosan, dextran, gelatin, lectins, and sodium alginate (Tekade R.K. and Chougule M.B., 2013, Tekade R.K. et al, 2014, Youngren S.R. et al, 2013).…”

Section: Non-viral Delivery Of Sirna To the Lungmentioning

confidence: 99%

Aerosol Delivery of siRNA to the Lungs. Part 2: Nanocarrier-based Delivery Systems

Youngren-Ortiz

Gandhi

España-Serrano

et al. 2017

KONA

Self Cite

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In this article, applications of engineered nanoparticles containing siRNA for inhalation delivery are reviewed and discussed. Diseases with identified protein malfunctions may be mitigated through the use of well-designed siRNA therapeutics. The inhalation route of administration provides local delivery of siRNA therapeutics to the lungs for various pulmonary diseases. A siRNA delivery system can be used to overcome the barriers of pulmonary delivery, such as anatomical barriers, mucociliary clearance, cough clearance, and alveolar macrophage clearance. Apart from naked siRNA aerosol delivery, previously studied siRNA carrier systems include those of lipidic, polymeric, peptide, or inorganic origin. These delivery systems can achieve pulmonary delivery through the generation of an aerosol via an inhaler or nebulizer. The preparation methodologies for these siRNA nanocarrier systems will be discussed herein. The use of inhalable nanocarrier siRNA delivery systems have barriers to their effective delivery, but overcoming these constraints while formulating a safe and effective delivery system will offer unique advances to the field of inhaled medicine.

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STAT6 siRNA Matrix-Loaded Gelatin Nanocarriers: Formulation, Characterization, andEx VivoProof of Concept Using Adenocarcinoma Cells

Cited by 71 publications

References 90 publications

miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

Dendrimer, Liposomes, Carbon Nanotubes and PLGA Nanoparticles: One Platform Assessment of Drug Delivery Potential

Aerosol Delivery of siRNA to the Lungs. Part 2: Nanocarrier-based Delivery Systems

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