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Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles

ABSTRACT: Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles

PROVIDER: PRJNA1035764 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26668520_1.fastq.gz	Fastqsanger.gz
	SRR26668520_2.fastq.gz	Fastqsanger.gz
	SRR26668521_1.fastq.gz	Fastqsanger.gz
	SRR26668521_2.fastq.gz	Fastqsanger.gz
	SRR26668522_1.fastq.gz	Fastqsanger.gz

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Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles

Project description:In the present study, we designed a nanoscale platform for the sustained and controlled delivery of nutrients to pancreatic islets-upon transplantation. Our platform consists of a mesoporous silica nanoparticle (MSNP), loaded with glutamine (G), an essential amino acid required for islet survival and function, and capped with polydopamine (PD). To control the release of glutamine, various concentrations (0.5 - 2 mg/mL) of PD and incubation times (0.5 – 2 h) with MSNPs were investigated in terms of pharmacological properties and biological functions. After extensive testing, PD-G-MSNPs made using PD coating of 0.5 mg/mL incubated for 0.5 h resulted in the optimal platform to maintain the islet viability and functionality in vitro. Following syngeneic renal sub-capsule islet transplantation in STZ-diabetic mice, PD-G-MSNPs improved the engraftment of pancreatic islets as well as their function, resulting in re-establishment of glycemic control. Collectively, our data shows that PD-G-MSNPs can support transplanted islets by providing them with a controlled and sustained supply of nutrients.

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Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles.

Project description:In the present study, we created a nanoscale platform that can deliver nutrients to pancreatic islets in a controlled manner. Our platform consists of a mesoporous silica nanoparticle (MSNP), which can be loaded with glutamine (G: an essential amino acid required for islet survival and function). To control the release of G, MSNPs were coated with a polydopamine (PD) layer. With the optimal parameters (0.5 mg/mL and 0.5 h), MSNPs were coated with a layer of PD, which resulted in a delay of G release from MSNPs over 14 d (57.4 ± 4.7% release). Following syngeneic renal subcapsule islet transplantation in diabetic mice, PDG-MSNPs improved the engraftment of islets (i.e., enhanced revascularization and reduced inflammation) as well as their function, resulting in re-establishment of glycemic control. Collectively, our data show that PDG-MSNPs can support transplanted islets by providing them with a controlled and sustained supply of nutrients.

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Global gene expression analysis of macrophage response induced by nonporous and porous silica nanoparticles

Project description:Little is known about the global gene expression profile of macrophages in response to changes in size and porosity of silica nanoparticles (SNPs). Spherical nonporous SNPs of two different diameters, and mesoporous spherical SNPs with comparable size were characterized. Reactive oxygen species, mitochondrial membrane potential, lysosome degradation capacity, and lysosome pH were measured to evaluate the influence of nonporous and mesoporous SNPs on mitochondrial and lysosomal function. RNA-sequencing was utilized to generate transcriptional profiles of RAW264.7 macrophages exposed to non-toxic SNP doses. DESeq2, limma, and BinReg2 software were used to analyze the data based on both unsupervised and supervised strategies to identify genes with greatest differences among NP treatments. Utilizing GATHER and DAVID software, possible induced pathways were studied. We found that mesoporous silica nanoparticles are capable of altering gene expression in macrophages at doses that do not elicit acute cytotoxicity, while gene transcription was minimally affected by nonporous SNPs.

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