Apatite nanoparticle(sCA)-siTIMP1 delivery in NIH3T3
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE128124 | GEO | 2020/08/27
REPOSITORIES: GEO
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Project description:Apatite nanoparticle(sCA)-siTIMP1 delivery in NIH3T3
| PRJNA526507 | ENA
Project description:RNA interference (RNAi) has immense potential to modulate cell functions. However, effective delivery of siRNA while avoiding deleterious side effects has proven challenging. This study investigates both intended and unintended effects of diblock copolymer nanoparticle (NP) delivery of siRNA delivery to human mesenchymal stem cells (hMSC). Specifically, siRNA delivery was investigated at a range of NP-siRNA:hMSC ratios with a focus on the effects of NP-siRNA treatment on hMSC functions. Additionally, next-generation RNA sequencing (RNA-seq) was used with enrichment analysis to observe side effects in hMSC gene expression. Results show NP-siRNA delivery is negatively correlated with hMSC density. However, higher NP-siRNA:hMSC ratios increased cytotoxicity and decreased metabolic activity. hMSC proliferation was largely unaffected by NP-siRNA treatment, except for a 3-fold reduction in hMSCs seeded at 4,000 cells/cm2. Flow cytometry reveals that apoptosis is a function of NP-siRNA treatment time and seeding density; ~14% of the treated hMSCs seeded at 8,000 cells/cm2 were annexin V+-siRNA+ 24 h after treatment, while 11% of the treated population was annexin V+-siRNA-. RNA-seq shows that NP-siRNA treatment results in transcriptomic changes in hMSCs, while pathway analysis shows upregulation of apoptosis signaling and downregulation of metabolism, cell cycle, and DNA replication pathways, as corroborated by apoptosis, metabolism, and proliferation assays. Additionally, multiple innate immune signaling pathways such as toll-like receptor (TLR), retinoic acid-inducible gene 1 (RIG-I)-like receptor, and nuclear factor-κB (NF-κB) signaling pathways are upregulated. Furthermore, and consistent with traditional siRNA immune activation, cytokine-cytokine receptor signaling was also upregulated. Overall, this study provides insight into NP-siRNA:hMSC ratios that are favorable for siRNA delivery. Moreover, NP-siRNA delivery results in side effects across the MSC transcriptome that suggest activation of the innate immunity that could alter MSC functions associated with their therapeutic potential.
2016-09-30 | GSE87497 | GEO
Project description:Nanoparticles and nano delivery systems are continuously being refined and developed as means of treating numerous human diseases by site-specific, and target-oriented delivery of medicines. The nanoparticles can carry therapeutic cargo or be medicinal themselves by virtue of their constitutional structural components. Here we report the ability of synthetic N-acylethanolamides, linoleoylethanolamide (LEA) and oleoylethanolamide (OEA), with endocannabinoid-like activity, to form spherical colloidal nanoparticles that when conjugated with tissue specific homing molecules, can localise to specific areas of the body, and reduce inflammation. The opportunities to mediate pharmacological effects of endocannabinoids at targeted sites provides a novel drug delivery system with increased medicinal potential to treat many diseases in many areas of medicine.
2022-10-19 | GSE206164 | GEO
Project description:Purpose: A super carbonate apatite (sCA) nanoparticle is an in vivo pH-sensitive delivery system for siRNA and microRNA. These carriers accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Systemic administration of sCA incorporating siRNA and microRNA has demonstrated superb tumor suppressive effects in vivo. We recently observed that sCA could deliver abundant nucleic acids to the inflammatory sites in rheumatoid arthritis mouse model. Based on the success, we tried to examine whether sCA could deliver sufficient amounts of miRNA into the colorectum inflamed by dextran sodium sulfate (DSS) treatment. Methods: We performed a RNA sequencing analysis of the DSS-treated colon walls. DSS was administered for 4 days and sCA-miR-29a, sCA-miR-29b, sCA-NC-miR was injected on days 1, 2, 3. On day 4, colorectum was removed and the mRNA samples were subject to the RNA sequencing analysis. Results: RNA sequencing of the rectum samples showed a number of enhanced or reduced gene expression in DSS treated NC-miR group on day 4 compared to normal mice. Such tendency of upregulation or downregulation was also noted in DSS-treated NC-miR group on day 2. Comparison of DSS treated samples on day 4 among NC-miR, miR-29a and miR-29b groups, revealed that several gene expression related to the interferon pathway was reversed by miR-29a or miR-29b towards the normal controls. These include Stat1, Stat2, IRF7, IRF9, and IFIT1. Conclusions: Many molecules in the interferon signaling pathway were activated in DSS-induced colitis on day 4 and Stat1, Stat2, IRF7, IRF9, and IFIT1 were key molecules in the interferon related pathways. These findings suggest that sCA-miR-29a or sCA-miR-29b may inhibit type 1 IFN and type 2 IFN pathways which are otherwise activated by DSS treatment.
2018-08-10 | GSE93162 | GEO
Project description:Expression profiling of normal NIH3T3 and transformed NIH3T3 K-ras cell lines grown for 72 hours in optimal glucose availability (25 mM glucose) or low glucose availability (1 mM). Low glucose induces apoptosis in transformed cells as compared to normal ones.
2011-07-14 | GSE29962 | GEO
Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of lipid nanoparticles (LNPs) carrying mRNA in murine liver non parenchymal cells. We report that LNPs containing stereopure 20α-hydroxycholesterol (20α) deliver mRNA to these cells up to three-fold more efficiently than LNPs containing both 20α- and 20ß- hydroxycholesterols (20mix). We show from the sequencing data that 20mix LNPs were sorted into phagocytic pathways, resulting in different functional delivery between stereopure and non-stereopure LNPs. We performed scRNA-seq using the 10X Chromium System, loading ~2,000 cells per condition, and processed the resulting data using Cell Ranger, resulting in an average read depth of ~100,000 reads per cell. These data suggest that stereochemistry-dependent interactions between LNPs and target cells can be exploited to improve mRNA delivery.
2021-08-04 | GSE181333 | GEO
Project description:Transcriptional profiling of mouse NIH3T3 cells comparing control NIH3T3 cells transfected with a pEFm6-BRAF with cells transfected with pEFm6-BRAFV600E. Goal was to determine the effects of BRAFV600E gene transfection on global mouse NIH3T3 cells gene expression.
2017-01-01 | GSE90589 | GEO
Project description:While small interfering RNAs (siRNAs) have been rapidly appreciated to induce gene silencing, efficient vectors for primary cells and for systemic in vivo delivery are lacking. We here present a novel chemically modified cell-penetrating peptide named PepFect6 (PF6) for efficient delivery of siRNAs into various types of cells including e.g. lymphocyte suspension cells and primary embryonic stem cells. Stable PF6/siRNA nano- particles rapidly enter entire cell populations resulting in strong and persistent RNAi responses, without associated transcriptomic or proteomic changes. In contrast to the majority of chemical reagents, PF6-mediated delivery is independent of cell confluence and, in most cases, not significantly hampered by the presence of serum. Finally, strong RNAi responses are observed in two different in vivo models following systemic delivery of PF6/siRNA in mice. Taken together, PF6 is an efficient siRNA delivery vector with superior delivery properties as compared to other tested transfection reagents.
2009-12-31 | GSE19702 | GEO
Project description:Alveolar type II cells were isolated from mice before P. aeruginosa injection (basal state) and at 72 h post-PA, and were separated into Sca-1+ and Sca-1- populations. Gene expression profile in the following four groups of cells were compared: non-PA Sca-1-, non-PA Sca-1+, 72 h post-PA Sca-1- and 72 h post-PA Sca-1+.
2014-12-31 | GSE47600 | GEO