Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles.
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ABSTRACT:
SUBMITTER: Razavi M
PROVIDER: S-EPMC8121116 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
2023-12-04 | GSE247020 | GEO
Project description:Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles
| PRJNA1035764 | ENA
Project description:Drug-delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with controllable drug-release systems (DRSs) is still in its nascent stage. In this paper, we designed a two-way controlled drug-release system that can be promoted and prolonged, using the external stimulation of near-infrared light (NIR) and protein coating. A hierarchical nanostructure was fabricated using upconversion nanoparticles (UCNPs)-mesoporous silica as the core-shell structure with protein lysozyme coating. The mesoporous silica shell provides abundant pores for the loading of drug molecules and a specific type of photosensitive molecules. The morphology and the physical properties of the nanostructures were thoroughly characterized. The results exhibited the uniform core-shell nanostructures of ~four UCNPs encapsulated in one mesoporous silica nanoparticle. The core-shell nanoparticles were in the spherical shape with an average size of 200 nm, average surface area of 446.54 m2/g, and pore size of 4.6 nm. Using doxorubicin (DOX), a chemotherapy agent as the drug model, we demonstrated that a novel DRS with capacity of smart modulation to promote or inhibit the drug release under NIR light and protein coating, respectively. Further, we demonstrated the therapeutic effect of the designed DRSs using breast cancer cells. The reported novel controlled DRS with dual functionality could have a promising potential for chemotherapy treatment of solid cancers.
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Project description:The immediate release of chemotherapeutics at the target site, along with no premature release in circulation is always challenging. The purpose of this study was to develop a stimuli responsive drug delivery system, composed of lipid supported mesoporous silica nanoparticles (MSNPs) for triggered drug release at the target site and simultaneously avoiding the premature release. MSNPs with a higher drug loading capacity and very slow release were designed so as to enhance release by FDA approved US-irradiation. Doxorubicin, as a model drug, and perfluoropentane (PFP) as a US responsive material, were entrapped in the porous structure of MSNPs. Lipid coating enhanced the cellular uptake and in addition provided a gatekeeping effect at the pore opening to reduce premature release. The mechanical and thermal effects of US induced the conversion of liquid PFP to a gaseous form that was able to rupture the lipid layer, resulting in triggered drug release. The prolonged stability profile and non-toxic behavior made them suitable candidate for the delivery of anticancer drugs. This smart system, with the abilities of better cellular uptake and higher cytotoxic effects on US-irradiation, would be a good addition to the applied side of chemotherapeutic advanced drug delivery systems.
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Project description:Urgent intervention is required to improve the 5 year survival rate of pancreatic ductal adenocarcinoma (PDAC). While the four-drug regimen, FOLFIRINOX (comprising irinotecan, 5-fluorouracil, oxaliplatin, and leucovorin), has a better survival outcome than the more frequently used gemcitabine, the former treatment platform is highly toxic and restricted for use in patients with good performance status. Since irinotecan contributes significantly to FOLFIRINOX toxicity (bone marrow and gastrointestinal tract), our aim was to reduce the toxicity of this drug by a custom-designed mesoporous silica nanoparticle (MSNP) platform, which uses a proton gradient for high-dose irinotecan loading across a coated lipid bilayer (LB). The improved stability of the LB-coated MSNP (LB-MSNP) carrier allowed less drug leakage systemically with increased drug concentrations at the tumor sites of an orthotopic Kras-derived PDAC model compared to liposomes. The LB-MSNP nanocarrier was also more efficient for treating tumor metastases. Equally important, the reduced leakage and slower rate of drug release by the LB-MSNP carrier dramatically reduced the rate of bone marrow, gastrointestinal, and liver toxicity compared to the liposomal carrier. We propose that the combination of high efficacy and reduced toxicity by the LB-MSNP carrier could facilitate the use of irinotecan as a first-line therapeutic to improve PDAC survival.
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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??g?ml-1. DOX-loaded GSH-sensitive nanospheres containing 6??g?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??g?ml-1.
| S-EPMC6008237 | biostudies-literature
Project description:Mesoporous silica nanoparticles (MSNs) have been widely studied as drug delivery systems in nanomedicine. Surface coating of MSNs have enabled them to perform efficiently in terms of bioavailability, biocompatibility, therapeutic efficacy and targeting capability. Recent studies have suggested the use of polydopamine (PDA) as a facilitative coating for MSNs that provides sustained and pH-responsive drug release, owing to the adhesive "molecular-glue" function of PDA. This further endows these hybrid MSN@PDA particles with the ability to carry large amounts of hydrophilic drugs. In this study, we expand the feasibility of this platform in terms of exploring its ability to also deliver hydrophobic drugs, as well as investigate the effect of particle shape on intracellular delivery of both a hydrophilic and hydrophobic anticancer drug. MSN@PDA loaded with doxorubicin (hydrophilic) and fingolimod (hydrophobic) was studied via a systematic in vitro approach (cellular internalization, intracellular drug distribution and cytotoxicity). To promote the cellular uptake of the MSN@PDA particles, they were further coated with a polyethylene imine (PEI)-polyethylene glycol (PEG) copolymer. Drug-loaded, copolymer-coated MSN@PDA showed effective cellular uptake, intracellular release and an amplified cytotoxic effect with both doxorubicin and fingolimod. Additionally, rods exhibited delayed intracellular drug release and superior intracellular uptake compared to spheres. Hence, the study provides an example of how the choice and design of drug delivery systems can be tuned by the need for performance, and confirms the PDA coating of MSNs as a useful drug delivery platform beyond hydrophilic drugs.
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Project description:Cancer immunotherapy involves a cascade of events that ultimately leads to cytotoxic immune cells effectively identifying and destroying cancer cells. Responsive nanomaterials, which enable spatiotemporal orchestration of various immunological events for mounting a highly potent and long-lasting antitumor immune response, are an attractive platform to overcome challenges associated with existing cancer immunotherapies. Here, we report a multifunctional near-infrared (NIR)-responsive core-shell nanoparticle, which enables (i) photothermal ablation of cancer cells for generating tumor-associated antigen (TAA) and (ii) triggered release of an immunomodulatory drug (gardiquimod) for starting a series of immunological events. The core of these nanostructures is composed of a polydopamine nanoparticle, which serves as a photothermal agent, and the shell is made of mesoporous silica, which serves as a drug carrier. We employed a phase-change material as a gatekeeper to achieve concurrent release of both TAA and adjuvant, thus efficiently activating the antigen-presenting cells. Photothermal immunotherapy enabled by these nanostructures resulted in regression of primary tumor and significantly improved inhibition of secondary tumor in a mouse melanoma model. These biocompatible, biodegradable, and NIR-responsive core-shell nanostructures simultaneously deliver payload and cause photothermal ablation of the cancer cells. Our results demonstrate potential of responsive nanomaterials in generating highly synergistic photothermal immunotherapeutic response.
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Project description:Multifunctional drug carriers have great applications in biomedical field. In this study, we introduced both polydopamine (PDA) and zwitterionic polymer of poly(3-(3-methacrylamidopropyl-(dimethyl)-ammonio)propane-1-sulfonate) (PSPP) onto the surface of mesoporous silica nanoparticles (MSNs) to develop a novel nanoparticle (MSNs@PDA-PSPP), which was employed as a new kind of drug carrier for the delivery of doxorubicin (DOX). The PDA coating, as a gatekeeper, could endow the drug carrier with pH-sensitive drug release performance. The outermost PSPP layer would make the drug carrier possess protein resistance performance. The chemical structure and properties were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). MSNs@PDA-PSPP could keep good colloidal stability within 72 h in phosphate buffered saline (PBS) and protein solutions. Meanwhile, MSNs@PDA-PSPP exhibited a high drug loading for DOX. In vitro drug release experiments suggested MSNs-DOX@PDA-PSPP exhibited pH-dependent drug release behaviors. Besides, MSNs@PDA-PSPP had no cytotoxicity to human hepatocellular carcinoma cells (HepG2 cells) even at a concentration of 125 µg/mL. More importantly, cellular uptake and in vitro anticancer activity tests suggested that MSNs-DOX@PDA-PSPP could be taken up by HepG2 cells and DOX could be successfully released and delivered into the cell nuclei. Taken together, MSNs@PDA-PSPP have great potential in the biomedical field.
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Project description:Microfluidics has become a popular method for constructing nanosystems in recent years, but it can also be used to coat other materials with polymeric layers. The polymeric coating may serve as a diffusion barrier against hydrophilic compounds, a responsive layer for controlled release, or a functional layer introduced to a nanocomposite for achieving the desired surface chemistry. In this study, mesoporous silica nanoparticles (MSNs) with enlarged pores were synthesized to achieve high protein loading combined with high protein retention within the MSN system with the aid of a microfluidic coating. Thus, MSNs were first coated with a cationic polyelectrolyte, poly (diallyldimethylammonium chloride) (PDDMA), and to potentially further control the protein release, a second coating of a pH-sensitive polymer (spermine-modified acetylated dextran, SpAcDEX) was deposited by a designed microfluidic device. The protective PDDMA layer was first formed under aqueous conditions, whereby the bioactivity of the protein could be maintained. The second coating polymer, SpAcDEX, was preferred to provide pH-sensitive protein release in the intracellular environment. The optimized formulation was effectively taken up by the cells along with the loaded protein cargo. This proof-of-concept study thus demonstrated that the use of microfluidic technologies for the design of protein delivery systems has great potential in terms of creating multicomponent systems and preserving protein stability.
| S-EPMC8946851 | biostudies-literature