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A polyoxyethylene sorbitan oleate modified hollow gold nanoparticle system to escape macrophage phagocytosis designed for triple combination lung cancer therapy via LDL-R mediated endocytosis.

ABSTRACT: Presently, a combination of chemotherapy, radiotherapy, thermotherapy, and other treatments has become a hot topic of research for the treatment of cancer, especially lung cancer. In this study, novel hollow gold nanoparticles (HGNPs) were used as drug carriers, and in order to improve the targeting ability of HGNPs to a lung tumor site, polyoxyethylene sorbitol oleate (PSO) was chosen here as a target ligand since it can be specifically recognized by the low-density lipoprotein (LDL) receptor which is usually over expressed on A549 lung cancer cells. In this way, a PSO-modified doxorubicin-loaded HGNP drug delivery system (PSO-HGNPs-DOX) was constructed and its physicochemical properties, photothermal conversion ability, and drug release of PSO-HGNPs-DOX was investigated. Further, the effects of triple combination therapy, the intracellular uptake, and the ability to escape macrophage phagocytosis of PSO-HGNPs-DOX were also studied using A549 cells in vitro. In addition, an in vivo mouse model was also used to study the targeting of PSO-HGNPs-DOX to lung cancer. PSO-HGNPs-DOX demonstrated a good triple therapeutic effect for lung cancer (A549 cell viability was only 10% at 500 μM) by LDL receptor mediated endocytosis and was able to escape macrophage phagocytosis to enhance its accumulation at the target site. Therefore, PSO-HGNPs-DOX is a novel, safe, promising, and targeted drug carrier designed for triple combination lung cancer therapy which should be further studied for such applications.

SUBMITTER: Shen Y

PROVIDER: S-EPMC7534200 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The synthesis and development of poly(ε-caprolactone) conjugated polyoxyethylene sorbitan oleate-based micelles for curcumin drug release: an <i>in vitro</i> study on breast cancer cells.

Project description:Backgroundit is now known that curcumin (Cur) has a broad range of biological properties; however, photosensitivity, as well as low bioavailability and short half-life, have limited its clinical application. To overcome these problems the synthesis of poly(ε-caprolactone)-Tween 80 (PCL-T) copolymers was performed.Methodsthe copolymers of PCL-T were created using the solvent evaporation/extraction technique. Then Cur was loaded in PCL-T micelles (PCL-T-M) by a self-assembly method. The characterization of copolymer and micelles was assessed by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1HNMR), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and dynamic light scattering (DLS) methods. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was used to indicate the cytotoxicity of the free Cur, PCL-T-M, and Cur-loaded PCL-T-M.ResultsTEM analysis showed monodispersed and spherical shapes with a size of about 90 nm. Cur was released from PCL-T-M at pH 7.4 (45%) and 5.5 (90%) during 6 days. After 24 and 48 h, the IC50 of the free Cur, PCL-T-M, and Cur-loaded PCL-T-M on MCF-7 cells were 80.86 and 54.45 μg mL-1, 278.30 and 236.19 μg mL-1, 45.47 and 19.05 μg mL-1, respectively.Conclusionthis study showed that, in the same concentration, the effectiveness of the Cur-loaded PCL-T-M is more than the free Cur, and the nano-system has been able to overcome delivery obstacles of Cur drug. Thus, PCL-T-M can be a candidate as a drug carrier for the delivery of Cur and future therapeutic investigations on breast cancer.

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| S-EPMC5997900 | biostudies-literature

Stabilisation of Lutein and Lutein Esters with Polyoxyethylene Sorbitan Monooleate, Medium-Chain Triglyceride Oil and Lecithin.

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High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans.

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| S-EPMC4346138 | biostudies-literature

Nanoparticle stereochemistry-dependent endocytosis improves in vivo mRNA delivery

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

LDL particle core enrichment in cholesteryl oleate increases proteoglycan binding and promotes atherosclerosis.

Project description:Several studies in humans and animals suggest that LDL particle core enrichment in cholesteryl oleate (CO) is associated with increased atherosclerosis. Diet enrichment with MUFAs enhances LDL CO content. Steroyl O-acyltransferase 2 (SOAT2) is the enzyme that catalyzes the synthesis of much of the CO found in LDL, and gene deletion of SOAT2 minimizes CO in LDL and protects against atherosclerosis. The purpose of this study was to test the hypothesis that the increased atherosclerosis associated with LDL core enrichment in CO results from an increased affinity of the LDL particle for arterial proteoglycans. ApoB-100-only Ldlr(-/-) mice with and without Soat2 gene deletions were fed diets enriched in either cis-MUFA or n-3 PUFA, and LDL particles were isolated. LDL:proteogylcan binding was measured using surface plasmon resonance. Particles with higher CO content consistently bound with higher affinity to human biglycan and the amount of binding was shown to be proportional to the extent of atherosclerosis of the LDL donor mice. The data strongly support the thesis that atherosclerosis was induced through enhanced proteoglycan binding of LDL resulting from LDL core CO enrichment.

| S-EPMC3735946 | biostudies-literature

BMP-9 and LDL crosstalk regulates ALK-1 endocytosis and LDL transcytosis in endothelial cells.

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| S-EPMC7939458 | biostudies-literature

Microcalorimetric method to assess phagocytosis: macrophage-nanoparticle interactions.

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Nanoparticle-Induced Augmentation of Neutrophils' Phagocytosis of Bacteria.

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| S-EPMC9289463 | biostudies-literature

Nanoparticle elasticity regulates phagocytosis and cancer cell uptake.

Project description:The ability of cells to sense external mechanical cues is essential for their adaptation to the surrounding microenvironment. However, how nanoparticle mechanical properties affect cell-nanoparticle interactions remains largely unknown. Here, we synthesized a library of silica nanocapsules (SNCs) with a wide range of elasticity (Young's modulus ranging from 560 kPa to 1.18 GPa), demonstrating the impact of SNC elasticity on SNC interactions with cells. Transmission electron microscopy revealed that the stiff SNCs remained spherical during cellular uptake. The soft SNCs, however, were deformed by forces originating from the specific ligand-receptor interaction and membrane wrapping, which reduced their cellular binding and endocytosis rate. This work demonstrates the crucial role of the elasticity of nanoparticles in modulating their macrophage uptake and receptor-mediated cancer cell uptake, which may shed light on the design of drug delivery vectors with higher efficiency.

| S-EPMC7164958 | biostudies-literature

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