Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Razavi M

PROVIDER: S-EPMC8121116 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Razavi Mehdi M Primavera Rosita R Kevadiya Bhavesh D BD Wang Jing J Ullah Mujib M Buchwald Peter P Thakor Avnesh S AS

Nano letters 20200921 10

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 rel ...[more]

PMID: 32909757

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Project description:Tunable glutathione (GSH)-sensitive hollow mesoporous silica nanoparticles (HMSiO2 NPs) were developed using a structural difference-based selective etching strategy. These organosilica hollow nanoparticles contained disulfide linkages (S-S) in the outer shell which were degraded by GSH. The particles were compared with their nonGSH-sensitive tetraethyl orthosilicate (TEOS) HMSiO2 counterparts in terms of their synthesis method, characterization, doxorubicin (DOX) release profile, and in vitro cytotoxicity in MCF-7 breast cancer cells. Transmission electron microscopy (TEM) of the particles indicated that the fabricated HMSiO2 NPs had an average diameter of 130 ± 5 nm. Thermogravimetric analysis (TGA) revealed that GSH-sensitive particles had approximately 5.3% more weight loss than TEOS HMSiO2 NPs. Zeta potential of these redox-responsive particles was -23 ± 1 mV at pH 6 in deionized (DI) water. Nitrogen adsorption-desorption isotherm revealed that the surface area of the hollow mesoporous nanoreservoirs was roughly 446 ± 6 m2 g-1 and the average diameter of the pores was 2.3 ± 0.5 nm. TEM images suggest that the nanoparticles started to lose mass integrity from Day 1. The particles showed a high loading capacity for DOX (8.9 ± 0.5%) as a model drug, due to the large voids existing in the hollow structures. Approximately 58% of the incorporated DOX released within 14 days in phosphate buffered saline (PBS) at pH 6 and in the presence of 10 mM of GSH, mimicking intracellular tumor microenvironment while release from TEOS HMSiO2 NPs was only c.a. 18%. The uptake of these hollow nanospheres by MCF-7 cells and RAW 264.7 macrophages was evaluated using TEM and confocal microscopy. The nanospheres were shown to accumulate in the endolysosomal compartments after incubation for 24 h with the maximum uptake of c.a. 2.1 ± 0.3% and 5.2 ± 0.4%, respectively. Cytotoxicity of the nanospheres was investigated using CCK-8 assay. Results indicate that intact hollow particles (both GSH-sensitive and TEOS HMSiO2 NPs) were nontoxic to MCF-7 cells after incubation for 24 h within the concentration range of 0-1000 μg ml-1. DOX-loaded GSH-sensitive nanospheres containing 6 μg ml-1 of DOX killed c.a. 51% of MCF-7 cells after 24 h while TEOS HMSiO2 NPs killed c.a. 20% with the difference being statistically significant. Finally, cytotoxicity data in RAW 264.7 macrophages and NIH 3 T3 fibroblasts shows that intact GSH-sensitive HMSiO2 NPs did not show any toxic effects on these cells with the concentrations equal or <125 μg ml-1.

Dataset Information

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

Publications

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

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