Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method.

ABSTRACT: In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To further improve the efficiency of tumor delivery and avoid liver toxicity, we successfully developed an inorganic nanoparticle device (iNaD) via high-frequency ultrasonic pulverization combined with PEG blending during the production of sCA. Compared to sCA loaded with 24 μg of miRNA, systemic administration of iNaD loaded with 0.75 μg of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 μg of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 μg. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering.

SUBMITTER: Wu X

PROVIDER: S-EPMC8623677 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

A Method to Encapsulate Small Organic Molecules in Calcium Phosphate Nanoparticles Based on the Supramolecular Chemistry of Cyclodextrin.

Project description:Calcium phosphate nanoparticles (CPNPs) encapsulating small organic molecules, such as imaging agents and drugs, are considered to be ideal devices for cancer diagnosis or therapy. However, it is generally difficult to encapsulate small organic molecules in CPNPs because of the lack of solubility in water or binding affinity to calcium phosphate. To solve these issues, we utilized the carboxymethyl ?-cyclodextrin (CM-?-CD) to increase the solubility and binding affinity to small organic molecules for the encapsulation into CPNPs in this work. The results indicated that the model molecules, hydrophilic rhodamine B (RB) and hydrophobic docetaxel (Dtxl), are successfully encapsulated into CPNPs with the assistance of CM-?-CD. We also demonstrated the CPNPs could be remarkably internalized into A549 cells, resulting in the efficient inhibition of tumor cells' growth.

| S-EPMC6190105 | biostudies-literature

A Valid Bisphosphonate Modified Calcium Phosphate-Based Gene Delivery System: Increased Stability and Enhanced Transfection Efficiency In Vitro and In Vivo.

Project description:Calcium phosphate (CaP) nanoparticles, as a promising vehicle for gene delivery, have been widely used owing to their biocompatibility, biodegradability and adsorptive capacity for nucleic acids. Unfortunately, their utility in vivo has been profoundly restricted due to numerous technical barriers such as the lack of tissue specificity and limited transfection efficiency, as well as uncontrollable aggregation over time. To address these issues, an effective conjugate folate-polyethylene glycol-pamidronate (shortened as FA-PEG-Pam) was designed and coated on the surface of CaP/NLS/pDNA (CaP/NDs), forming a versatile gene carrier FA-PEG-Pam/CaP/NDs. Inclusion of FA-PEG-Pam significantly reduced the size of CaP nanoparticles, thus inhibiting the aggregation of CaP nanoparticles. FA-PEG-Pam/CaP/NDs showed better cellular uptake than mPEG-Pam/CaP/NDs, which could be attributed to the high-affinity interactions between FA and highly expressed FR. Meanwhile, FA-PEG-Pam/CaP/NDs had low cytotoxicity and desired effect on inducing apoptosis (71.1%). Furthermore, FA-PEG-Pam/CaP/NDs showed admirable transfection efficiency (63.5%) due to the presence of NLS peptides. What's more, in vivo studies revealed that the hybrid nanoparticles had supreme antitumor activity (IR% = 58.7%) among the whole preparations. Altogether, FA-PEG-Pam/CaP/NDs was expected to be a hopeful strategy for gene delivery.

| S-EPMC6781291 | biostudies-literature

Recent In Vivo Evidences of Particle-Based Delivery of Small-Interfering RNA (siRNA) into Solid Tumors.

Project description:Small-interfering RNA (siRNA) is both a powerful tool in research and a promising therapeutic platform to modulate expression of disease-related genes. Malignant tumors are attractive disease targets for nucleic acid-based therapies. siRNA directed against oncogenes, and genes driving metastases or angiogenesis have been evaluated in animal models and in some cases, in humans. The outcomes of these studies indicate that drug delivery is a significant limiting factor. This review provides perspectives on in vivo validated nanoparticle-based siRNA delivery systems. Results of recent advances in liposomes and polymeric and inorganic formulations illustrate the need for mutually optimized attributes for performance in systemic circulation, tumor interstitial space, plasma membrane, and endosomes. Physiochemical properties conducive to efficient siRNA delivery are summarized and directions for future research are discussed.

| S-EPMC4161233 | biostudies-literature

An improved method for surface immobilisation of RNA: application to small non-coding RNA-mRNA pairing.

Project description:Characterisation of RNA and its intermolecular interactions is increasing in importance as the inventory of known RNA functions continues to expand. RNA-RNA interactions are central to post-transcriptional gene regulation mechanisms in bacteria, and the interactions of bacterial small non-coding RNAs (sRNAs) with their mRNA targets are the subject of much current research. The technology of surface plasmon resonance (SPR) is an attractive approach to studying these interactions since it is highly sensitive, and allows interaction measurements to be recorded in real-time. Whilst a number of approaches exist to label RNAs for surface-immobilisation, the method documented here is simple, quick, efficient, and utilises the high-affinity streptavidin-biotin interaction. Specifically, we ligate a biotinylated nucleotide to the 3' end of RNA using T4 RNA ligase. Although this is a previously recognised approach, we have optimised the method by our discovery that the incorporation of four or more adenine nucleotides at the 3' end of the RNA (a poly-A-tail) is required in order to achieve high ligation efficiencies. We use this method within the context of investigating small non-coding RNA (sRNA)-mRNA interactions through the application of surface technologies, including quantitative SPR assays. We first focus on validating the method using the recently characterised Escherichia coli sRNA-mRNA pair, MicA-ompA, specifically demonstrating that the addition of the poly-A-tail to either RNA does not affect its subsequent binding interactions with partner molecules. We then apply this method to investigate the novel interactions of a Vibrio cholerae Qrr sRNA with partner mRNAs, hapR and vca0939; RNA-RNA pairings that are important in mediating pathogenic virulence. The calculated binding parameters allow insights to be drawn regarding sRNA-mRNA interaction mechanisms.

| S-EPMC3828260 | biostudies-literature

Biphasic composite of calcium phosphate-based mesoporous silica as a novel bone drug delivery system.

Project description:We reported the new biphasic composites of calcium phosphate and mesoporous silica material (CaP@MSi) in the form of powders and pellets as a potential bone drug delivery system for doxycycline hydrochloride (DOX). The CaP@MSi powders were synthesized by cationic surfactant-templating method. The effects of 10, 20, and 30% CaP content in the CaP@MSi powders on the molecular surface structure, the cytotoxicity against osteoblast cells in vitro, and the mineralization potential in simulated body fluid were investigated. The CaP@MSi characterized by the highest mineralization potential (30% CaP content) were used for DOX adsorption and pelletization process. The CaP which precipitated in the CaP@MSi composites was characterized as calcium-deficient with the Ca:P molar ratio between 1.0 and 1.2. The cytotoxicity assays demonstrated that the CaP content in MSi increases osteoblasts viability indicating the CaP@MSi (30% CaP content) as the most biocompatible. The combination of CaP and MSi was an effective strategy to improve the mineralization potential of parent material. Upon immersion in simulated body fluid, the CaP of composite converted into the bone-like apatite. The obtained pellets preserved the mineralization potential of CaP@MSi and provided the prolonged 5-day DOX release. The obtained biphasic CaP@MSi composites seem to have an application potential as bone-specific drug delivery system.

| S-EPMC7066108 | biostudies-literature

A method for in vivo identification of bacterial small RNA-binding proteins.

Project description:Small bacterial regulatory RNAs (sRNAs) have gained immense appreciation over the last decade for their roles in mediating posttranscriptional gene regulation of numerous physiological processes. Several proteins contribute to sRNA stability and regulation, most notably the Hfq RNA-binding protein. However, not all sRNAs rely on Hfq for their stability. It is therefore likely that other proteins contribute to the stability and function of certain bacterial sRNAs. Here, we describe a methodology for identifying in vivo-binding proteins of sRNAs, developed using the iron-responsive PrrF and PrrH sRNAs of Pseudomonas aeruginosa. RNA was isolated from iron-depleted cultures, which were irradiated to cross-link nucleoprotein complexes. Subsequently, PrrF- and PrrH-protein complexes were enriched using cDNA "bait", and enriched RNA-protein complexes were analyzed by tandem mass spectrometry to identify PrrF and PrrH associated proteins. This method identified Hfq as a potential PrrF- and PrrH-binding protein. Interestingly, Hfq was identified more often in samples probed with the PrrF cDNA "bait" as compared to the PrrH cDNA "bait", suggesting Hfq has a stronger binding affinity for the PrrF sRNAs in vivo. Hfq binding to the PrrF and PrrH sRNAs was validated by electrophoretic mobility shift assays with purified Hfq protein from P. aeruginosa. As such, this study demonstrates that in vivo cross-linking coupled with sequence-specific affinity chromatography and tandem mass spectrometry (SSAC-MS/MS) is an effective methodology for unbiased identification of bacterial sRNA-binding proteins.

| S-EPMC4263517 | biostudies-literature

Sustained delivery of calcium and orthophosphate ions from amorphous calcium phosphate and poly(L-lactic acid)-based electrospinning nanofibrous scaffold.

Project description:The purpose of this study is to investigate electrospinning poly(L-lactic acid) (PLLA) nanofibrous scaffold with different contents of amorphous calcium phosphate (ACP), which is suitable for using in bone regeneration through sustained release of calcium and orthophosphate ions. Three groups of nanofibrous scaffolds, ACP-free PLLA, ACP-5?wt%/PLLA and ACP-10?wt%/PLLA, are developed and characterized by scanning electron microscopy and gel permeation chromatography. Calcium and phosphate colorimetric assay kits are used to test ions released from scaffold during hydrolytic degradation. The results show ACP-5?wt%/PLLA and ACP-10?wt%/PLLA scaffolds have relatively high degradation rates than ACP-free PLLA group. The bioactivity evaluation further reveals that ACP-5?wt%/PLLA scaffold presents more biocompatible feature with pre-osteoblast cells and significant osteogenesis ability of calvarial bone defect. Due to the facile preparation method, sustained calcium and orthophosphate release behavior, and excellent osteogenesis capacity, the presented ACP/PLLA nanofibrous scaffold has potential applications in bone tissue engineering.

| S-EPMC5374505 | biostudies-literature

Synthetic amorphous magnesium-substituted calcium phosphate: silent constructs that trap macromolecules for intracellular delivery

Project description:Amorphous magnesium-substituted calcium phosphate (AMCP) nanoparticles form constitutively in large numbers in the gastrointestinal tract. Collective evidence indicates that they trap luminal macromolecules, such as bacterial and dietary protein antigen, delivering this cargo to mucosal antigen presenting cells. Here using a precise synthetic mimetic of the AMCP nanomineral, we studied whether trapping of macromolecules by AMCP modulates signalling of the macromolecule itself. Based upon whole genome transcriptomic analyses and using peptidoglycan as a macromolecule, we showed that neither AMCP nanomineral itself regulated any gene, nor did it modify any gene regulation by peptidoglycan. We conclude that synthetic AMCP nanomineral can deliver macromolecular cargo intracellularly without affecting gene transcription.

2022-06-01 | GSE59498 | GEO

Charge reversible calcium phosphate lipid hybrid nanoparticle for siRNA delivery.

Project description:Bcl-2 gene is an important target to treat lung cancer. The small interference RNA (siRNA) of Bcl-2 gene (siBcl-2) can specifically silence Bcl-2 gene. However, naked siBcl-2 is difficult to accumulate in the tumor tissue to exert its activity. In this paper, a calcium phosphate lipid hybrid nanoparticle that possessed charge reversible property was prepared to enhance the activity of siBcl-2 in vivo. The average diameter and zeta potential of siBcl-2 loaded calcium phosphate lipid hybrid nanoparticles (LNPS@siBcl-2) were 80 nm and -13 mV at pH7.4 whereas the diameter and zeta potential changed to 1506 nm and +9 mV at pH5.0. LNPS@siBcl-2 could efficiently deliver siBcl-2 to the cytoplasm and significantly decreased the expression of Bcl-2 in A549 cells. Moreover, the in vivo experimental results showed that most of the Cy5-siBcl-2 accumulated in tumor tissue after LNPS@Cy5-siBcl-2 was administered to tumor-bearing mice by tail vein injection. Meanwhile, the expression of Bcl-2 was decreased but the expression of the BAX and Caspase-3 was increased in tumor tissue. LNPS@siBcl-2 significantly inhibited the growth of tumor in tumor-bearing mice without any obvious systemic toxicity. Thus, the charge reversible calcium phosphate lipid hybrid nanoparticle was an excellent siBcl-2 delivery carrier to improve the activity of siBcl-2 in vivo. LNPS@siBcl-2 has potential in the treatment of lung cancer.

| S-EPMC5522105 | biostudies-literature

Mechanisms of in Vivo Degradation and Resorption of Calcium Phosphate Based Biomaterials.

Project description:Calcium phosphate ceramic materials are extensively used for bone replacement and regeneration in orthopedic, dental, and maxillofacial surgical applications. In order for these biomaterials to work effectively it is imperative that they undergo the process of degradation and resorption in vivo. This allows for the space to be created for the new bone tissue to form and infiltrate within the implanted graft material. Several factors affect the biodegradation and resorption of calcium phosphate materials after implantation. Various cell types are involved in the degradation process by phagocytic mechanisms (monocytes/macrophages, fibroblasts, osteoblasts) or via an acidic mechanism to reduce the micro-environmental pH which results in demineralization of the cement matrix and resorption via osteoclasts. These cells exert their degradation effects directly or indirectly through the cytokine growth factor secretion and their sensitivity and response to these biomolecules. This article discusses the mechanisms of calcium phosphate material degradation in vivo.

| S-EPMC5458904 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data