A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery

Wolfram, Joy; Nizzero, Sara; Liu, Haoran; Li, Feng; Zhang, Guodong; Zheng, Li; Shen, Haifa; Blanco, Elvin; Ferrari, Mauro

doi:10.1038/s41598-017-14221-2

Cited by 120 publications

(125 citation statements)

References 77 publications

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“…In this study, the potential protective effects of BiNPs against apoptotic (ethanol) and oxidative stress‐inducing (hydrogen peroxide) agents were assessed. Macrophages were chosen as an in vitro model of cell stress as the largest portion of intravenously administered nanoparticles (synthetic or biological) are internalized by circulating or resident macrophages 1,41–44. Moreover, macrophages play a major role in tissue regeneration and several studies have demonstrated that the depletion of these cells causes impaired tissue repair 45,46.…”

Section: Resultsmentioning

confidence: 99%

Adipose‐Derived Biogenic Nanoparticles for Suppression of Inflammation

Tian

Ticer

Wang

et al. 2020

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Extracellular vesicles secreted from adipose‐derived mesenchymal stem cells (ADSCs) have therapeutic effects in inflammatory diseases. However, production of extracellular vesicles (EVs) from ADSCs is costly, inefficient, and time consuming. The anti‐inflammatory properties of adipose tissue‐derived EVs and other biogenic nanoparticles have not been explored. In this study, biogenic nanoparticles are obtained directly from lipoaspirate, an easily accessible and abundant source of biological material. Compared to ADSC‐EVs, lipoaspirate nanoparticles (Lipo‐NPs) take less time to process (hours compared to months) and cost less to produce (clinical‐grade cell culture facilities are not required). The physicochemical characteristics and anti‐inflammatory properties of Lipo‐NPs are evaluated and compared to those of patient‐matched ADSC‐EVs. Moreover, guanabenz loading in Lipo‐NPs is evaluated for enhanced anti‐inflammatory effects. Apolipoprotein E and glycerolipids are enriched in Lipo‐NPs compared to ADSC‐EVs. Additionally, the uptake of Lipo‐NPs in hepatocytes and macrophages is higher. Lipo‐NPs and ADSC‐EVs have comparable protective and anti‐inflammatory effects. Specifically, Lipo‐NPs reduce toll‐like receptor 4‐induced secretion of inflammatory cytokines in macrophages. Guanabenz‐loaded Lipo‐NPs further suppress inflammatory pathways, suggesting that this combination therapy can have promising applications for inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

Adipose‐Derived Biogenic Nanoparticles for Suppression of Inflammation

Tian

Ticer

Wang

et al. 2020

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“…Kupffer cells are the macrophages with the strongest phagocytic capacity. Pretreatment of mice with chloroquine before administering NPs provided a straightforward approach to reduce the uptake by macrophages . Before administration of drug‐carrying NPs, consumption of the phagocytic ability of Kupffer cells by over‐injection of blank NPs sounds reasonable .…”

Section: Strategies To Reduce Np Uptake By the Mpsmentioning

confidence: 99%

New Strategies in the Design of Nanomedicines to Oppose Uptake by the Mononuclear Phagocyte System and Enhance Cancer Therapeutic Efficacy

Zhou

Dai

2018

Chemistry An Asian Journal

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The application of nanotechnology in the treatment of tumors has boomed owing to the vigorous development in cancer nanomedicine. Despite the great success achieved in this field, nanomedicine has not realized its full potential owing to a delivery barrier, the mononuclear phagocytic system (MPS), which cuts off more than 95 % of the administrated nanoparticles. This results in an extremely low drug-delivery efficacy to the tumor and leads to poor therapeutic outcomes. Moreover, the injection of excess nanoparticles also raises toxicity concerns induced by the accumulation of nanomaterials in organs, such as the liver and spleen. Therefore, a reduction in the uptake of nanomedicines by the MPS is vital to enhance the cancer therapeutic effect and decrease side effects. In this critical review, we will summarize the new strategies to reduce nanoparticle uptake by the MPS based on current knowledge of the bio-nano interaction. Further directions will also be highlighted for the development of cancer nanomedicine with a lower off-target rate and better therapeutic outcomes.

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“…67,68 As a gene delivery enhancing agent, chloroquine's ability to promote endolysosome escape has long been recognized. [69][70][71] Chloroquine can rapidly diffuse into cells where it can be trapped in endolysosomes, 72 and upon protonation and subsequent influx of water molecules, chloroquine can induce osmotic swelling of the endolysosome and endolysosome leakage. 73,74 Thus, we used chloroquine as a positive control for endolysosome leakage and determine the extent to which blocking TPCs affects endolysosome leakage.…”

Section: Tpcs Are Involved In Tat Endolysosome Escapementioning

confidence: 99%

Two‐pore channels regulate Tat endolysosome escape and Tat‐mediated HIV‐1 LTR transactivation

et al. 2020

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Abbreviations: BAPTA-AM, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester); CD26, cluster of differentiation 4; CD4+, cluster of differentiation 4; CNS, central nervous system; CRISPR, clustered regularly interspaced short palindromic repeats; CSF, cerebrospinal fluid; CXCR4, C-X-C chemokine receptor type 4; DMEM, Dulbecco's Modified Eagle Medium; FBS, fetal bovine serum; FITC, fluorescein isothiocyanate; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GFP, green fluorescent protein; gp120, envelope glycoprotein 120; HCl, hydrogen chloride; HIV-1, human immunodeficiency virus-1; kDa, kilodalton; LRP1, low density lipoprotein receptor-related protein 1; LTR, long terminal repeat; MERS-CoV, middle east respiratory syndrome coronavirus; MW, molecular weight; NAADP, nicotinic acid adenine dinucleotide phosphate; P2X4, purinergic P2X4 receptors; PAGE, polyacrylamide gel electrophoresis; PBS, phosphate-buffered saline; PI(3,5)P2, phosphatidylinositol 3,5-bisphosphate; PVDF, polyvinylidene difluoride; RIPA, radioimmunoprecipitation assay buffer; SD, standard deviation; SDS, sodium dodecyl sulfate; shRNA, short hairpin RNA; Tat, transcriptional activator; TFEB, transcription factor EB; TPCs, two-pore channels; Trans-Ned19, (1R,3S)-1- [3][4]piperazin-1-yl] methyl]-4-methoxyphenyl]-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid; TRPM2, transient receptor potential melastatin 2; TRPML1, transient receptor potential mucolipin 1. AbstractHIV-1 Tat is essential for HIV-1 replication and appears to play an important role in the pathogenesis of HIV-associated neurological complications. Secreted from infected or transfected cells, Tat has the extraordinary ability to cross the plasma membrane. In the brain, Tat can be taken up by CNS cells via receptor-mediated endocytosis. Following endocytosis and its internalization into endolysosomes, Tat must be released in order for it to activate the HIV-1 LTR promoter and facilitate HIV-1 viral replication in the nucleus. However, the underlying mechanisms whereby Tat escapes endolysosomes remain unclear. Because Tat disrupts intracellular calcium homeostasis, we investigated the involvement of calcium in Tat endolysosome escape and subsequent LTR transactivation. We demonstrated that chelating endolysosome calcium with high-affinity rhodamine-dextran or chelating cytosolic calcium with BAPTA-AM attenuated Tat endolysosome escape and LTR transactivation.Significantly, we demonstrated that pharmacologically blocking and knocking down the endolysosome-resident two-pore channels (TPCs) attenuated Tat endolysosome escape and LTR transactivation. This calcium-mediated effect appears to be selective for TPCs because knocking down TRPML1 calcium channels was without effect. Our findings suggest that calcium released from TPCs is involved in Tat endolysosome escape and subsequent LTR transactivation. TPCs might represent a novel therapeutic target against HIV-1 infection and HIV-associated neurological complications.

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A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery

Cited by 120 publications

References 77 publications

Adipose‐Derived Biogenic Nanoparticles for Suppression of Inflammation

Adipose‐Derived Biogenic Nanoparticles for Suppression of Inflammation

New Strategies in the Design of Nanomedicines to Oppose Uptake by the Mononuclear Phagocyte System and Enhance Cancer Therapeutic Efficacy

Two‐pore channels regulate Tat endolysosome escape and Tat‐mediated HIV‐1 LTR transactivation

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