213 results match your criteria agonist resiquimod

ABC triblock bottlebrush copolymer-based injectable hydrogels: design, synthesis, and application to expanding the therapeutic index of cancer immunochemotherapy.

Chem Sci 2020 Jun 1;11(23):5974-5986. Epub 2020 Jun 1.

Department of Chemistry, Massachusetts Institute of Technology Massachusetts 02139 USA

Bottlebrush copolymers are a versatile class of macromolecular architectures with broad applications in the fields of drug delivery, self-assembly, and polymer networks. Here, the modular nature of graft-through ring-opening metathesis polymerization (ROMP) is exploited to synthesize "ABC" triblock bottlebrush copolymers (TBCs) from polylactic acid (PLA), polyethylene glycol (PEG), and poly(-isopropylacrylamide) (PNIPAM) macromonomers. Due to the hydrophobicity of their PLA domains, these TBCs self-assemble in aqueous media at room temperature to yield uniform ∼100 nm micelles that can encapsulate a wide range of therapeutic agents. Read More

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A dual macrophage polarizer conjugate for synergistic melanoma therapy.

J Control Release 2021 May 25;335:333-344. Epub 2021 May 25.

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.

Tumor associated macrophages (TAMs) play a paradoxical role in the fate of aggressive tumors like melanoma. Immune modulation of TAMs from the tumor-permissive M2 phenotype to antitumoral M1 phenotype is an emerging attractive approach in melanoma therapy. Resiquimod is a TLR7/8 agonist that shifts the polarization of macrophages towards M1 phenotype. Read More

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Sustained IL-4 priming of macrophages enhances the inflammatory response to TLR7/8 ligand R848.

J Leukoc Biol 2021 May 19. Epub 2021 May 19.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

Macrophages (Mϕ) are highly plastic, and can acquire a variety of functional phenotypes depending on the presence of different stimuli in their local environment. Mφ stimulated by interleukin (IL)-4 induce an alternative activation state and function as anti-inflammatory cells and promote tissue repair. However, there is overwhelming evidence that IL-4 can play a role in promoting inflammation. Read More

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Polarization of Tumor-Associated Macrophages by Nanoparticle-Loaded Combined with Immunogenic Cell Death for Cancer Immunotherapy.

Nano Lett 2021 May 17;21(10):4231-4240. Epub 2021 May 17.

Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. China.

The tumor immunosuppressive microenvironment greatly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the tumor microenvironment, which can inhibit the tumor after converting it to an M1-like phenotype. In addition, immunogenic cell death (ICD) can increase the amount of T lymphocytes in tumors, activating antineoplastic immunity. Read More

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Q493K and Q498H substitutions in Spike promote adaptation of SARS-CoV-2 in mice.

EBioMedicine 2021 May 14;67:103381. Epub 2021 May 14.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China; Key Laboratory of development of veterinary diagnostic products, Ministry of Agriculture, Wuhan, 430070, PR China. Electronic address:

Background: An ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein .

Methods: SARS-CoV-2 was passaged in BALB/c mice to obtain mouse-adapted virus strain. Read More

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Toll-like receptor-7/8 agonist kill Leishmania amazonensis by acting as pro-oxidant and pro-inflammatory agent.

J Pharm Pharmacol 2021 May 3. Epub 2021 May 3.

Department of Chemistry and Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh, India.

Objectives: Evaluation of the anti-Leishmanial activity of imidazoquinoline-based TLR7/8 agonists.

Methods: TLR7/8-active imidazoquinolines (2 and 3) were synthesized and assessed for activity against Leishmania amazonensis-intracellular amastigotes using mouse peritoneal macrophages. The production of reactive oxygen species (ROS), nitric oxide (NO) and cytokines was determined in infected and non-infected macrophages. Read More

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Bioresorbable Depot for Sustained Release of Immunostimulatory Resiquimod in Suppressing Both Primary Triple-Negative Breast Tumors and Metastatic Occurrence.

Bioconjug Chem 2021 May 22;32(5):1008-1016. Epub 2021 Apr 22.

School of Bioengineering, Dalian University of Technology, No. 2 Linggong Road, Dalian 116024, China.

In light of immune facilities trafficking toward the pathological sites along upward gradient of immunostimulatory cytokines, a localized resiquimod (Toll-like receptor 7/8 agonist) release depot was manufactured for pursuit of precision immunostimulation toward intractable triple-negative breast carcinoma. In principle, resiquimod/poly(lactic--glycolic acid) microspheres were fabricated and embedded into injectable and biodegradable poly(ethylene glycol) (PEG)-based hydrogel. The subsequent investigations approved persistent retention of immunostimulatory resiquimod in tumors upon peritumoral administration, which consequently led to localized and consistent secretion of immunostimulatory cytokines. Read More

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Supramolecular assembly of Toll-like receptor 7/8 agonist into multimeric water-soluble constructs enables superior immune stimulation and .

ACS Appl Bio Mater 2020 May 8;3(5):3187-3195. Epub 2020 Apr 8.

Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, 20850, USA.

Resiquimod or R848 (RSQD) is a Toll-like receptor (TLR) 7/8 agonist which shows promise as vaccine adjuvant due to its potential to promote highly desirable cellular immunity. The development of this small molecule in the field to date has been largely impeded by its rapid clearance and lack of association with vaccine antigens. Here, we report a multimeric TLR 7/8 construct of nano-scale size, which results from a spontaneous self-assembly of RSQD with a water-soluble clinical-stage polymer - poly[di(carboxylatophenoxy)phosphazene] (PCPP). Read More

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Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment.

Int J Nanomedicine 2021 12;16:2775-2787. Epub 2021 Apr 12.

Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Purpose: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. Read More

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In vitro evidence suggesting that the toll-like receptor 7 and 8 agonist resiquimod (R-848) unlikely affects drug levels of co-administered compounds.

Eur J Pharm Sci 2021 Jul 2;162:105826. Epub 2021 Apr 2.

Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

Resiquimod (R-848) is an immune response modifier activating toll-like receptor 7 and 8. Its potential to cause pharmacokinetic interactions with concurrently administered drugs is unknown. To study the time course of the effect of resiquimod in LS180 cells as a model for intestinal tissue, luciferase-based reporter gene assays and reverse transcription polymerase chain reaction were used to investigate whether resiquimod affects the activities of nuclear factor kappa B (NF-ĸB), pregnane x receptor (PXR) or the transcription of selected central genes for drug disposition (cytochrome P-450 isozyme 3A4 (CYP3A4), CYP1A1, UDP-glucuronosyltransferase 1A1 (UGT1A1), ATP-binding cassette transporters ABCC2, ABCB1). Read More

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Tumor Activated Cell Penetrating Peptides to Selectively Deliver Immune Modulatory Drugs.

Pharmaceutics 2021 Mar 10;13(3). Epub 2021 Mar 10.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA 92093, USA.

Recent advances in immunotherapy have revolutionized cancer therapy. Immunotherapies can engage the adaptive and innate arms of the immune system. Therapeutics targeting immune checkpoint inhibitors (i. Read More

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Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors.

Nat Commun 2021 03 31;12(1):1999. Epub 2021 Mar 31.

Cello Therapeutics, Inc., San Diego, CA, 92121, USA.

Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. Read More

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4-phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model.

Exp Ther Med 2021 May 3;21(5):460. Epub 2021 Mar 3.

Division of Rheumatology, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Jeollabukdo 54907, Republic of Korea.

Impaired function of regulatory T cells (Tregs) contributes to the pathogenesis of systemic lupus erythematosus (SLE). Our previous study demonstrated aberrant responses of T lymphocytes to endoplasmic reticulum (ER) stress in patients with SLE. The present study investigated whether ER stress inhibition by 4-phenylbutyric acid (4-PBA) ameliorated lupus manifestations in an experimental lupus model and the effect of ER stress inhibition on the frequency and function of Tregs. Read More

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Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice.

ACS Nano 2021 03 1;15(3):4450-4466. Epub 2021 Mar 1.

Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland.

Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local delivery to specialized antigen-presenting cells (APCs). Multifunctional mesoporous silica nanoparticles (MSNs), with their large surface areas, their tunable particle and pore sizes, and their spatially controlled functionalization, represent a safe and versatile carrier system. In this study, we demonstrate the potential of MSNs as a pH-responsive drug carrier system for the anticancer immune-stimulant R848 (resiquimod), a synthetic Toll-like receptor 7 and 8 agonist. Read More

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Systemic Immunotherapy with Micellar Resiquimod-Polymer Conjugates Triggers a Robust Antitumor Response in a Breast Cancer Model.

Adv Healthc Mater 2021 05 1;10(10):e2100008. Epub 2021 Mar 1.

Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, Palo Alto, CA, 94305, USA.

Resiquimod is an immunopotent toll-like receptor 7/8 agonist with antitumor activity. Despite being potent against skin cancers, it is poorly tolerated systemically due to toxicity. Integrating resiquimod into nanoparticles presents an avenue to circumvent the toxicity problem. Read More

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Niclosamide suppresses the expansion of follicular helper T cells and alleviates disease severity in two murine models of lupus via STAT3.

J Transl Med 2021 02 25;19(1):86. Epub 2021 Feb 25.

The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Autoantibody production against endogenous cellular components is pathogenic feature of systemic lupus erythematosus (SLE). Follicular helper T (T) cells aid in B cell differentiation into autoantibody-producing plasma cells (PCs). The IL-6 and IL-21 cytokine-mediated STAT3 signaling are crucial for the differentiation to T cells. Read More

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February 2021

peripheral blood mononuclear cell response to R848 in children after supplementation with the probiotic NCFM/ Bi-07.

Benef Microbes 2021 Feb 8;12(1):85-93. Epub 2021 Feb 8.

Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53972, USA.

Several studies have demonstrated a decrease in upper respiratory infection (URI) frequency and severity in subjects taking probiotic supplements. We hypothesised beneficial effects of probiotics on viral URI in children are due to modulation of inflammatory innate immune responses. We tested this hypothesis, providing children with a probiotic combination of ssp. Read More

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February 2021

Cyclic Di-Adenosine Monophosphate: A Promising Adjuvant Candidate for the Development of Neonatal Vaccines.

Pharmaceutics 2021 Feb 1;13(2). Epub 2021 Feb 1.

Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.

Underdeveloped immunity during the neonatal age makes this period one of the most dangerous during the human lifespan, with infection-related mortality being one of the highest of all age groups. It is also discussed that vaccination during this time window may result in tolerance rather than in productive immunity, thus raising concerns about the overall vaccine-mediated protective efficacy. Cyclic di-nucleotides (CDN) are bacterial second messengers that are rapidly sensed by the immune system as a danger signal, allowing the utilization of these molecules as potent activators of the immune response. Read More

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February 2021

Use of TLR9 and TLR7/8 agonists in combination with d-galactosamine in exploring models for distinct severities of systemic inflammation relative to liver injury.

R Seki K Nishizawa

Physiol Res 2020 12 19;69(6):1125-1129. Epub 2020 Nov 19.

Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Tokyo, Japan.

Challenges with various TLR ligands (TLRLs)in combination with D-galactosamine (GalN) in rodents may mimic diverse conditions of acute inflammation and organ failure. Here, we report that CpG (ODN1826, TLR9 agonist)/GalN induced a liver-specific injury with modest systemic effects, whereas R848 (resiquimod, TLR7/8 agonist)/GalN exhibited systemic and liver toxicity. We also observed the protective effect of Gr-1+ cells (the population containing neutrophils) against liver injury in both the R848/GalN and CpG/GalN models. Read More

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December 2020

Development of thermosensitive resiquimod-loaded liposomes for enhanced cancer immunotherapy.

J Control Release 2021 Feb 13;330:1080-1094. Epub 2020 Nov 13.

Molecular Imaging Program, Department of Radiology, Stanford University, 3165 Porter Drive, Palo Alto, CA 94304, USA. Electronic address:

Resiquimod (R848) is a toll-like receptor 7 and 8 (TLR7/8) agonist with potent antitumor and immunostimulatory activity. However, systemic delivery of R848 is poorly tolerated because of its poor solubility in water and systemic immune activation. In order to address these limitations, we developed an intravenously-injectable formulation with R848 using thermosensitive liposomes (TSLs) as a delivery vehicle. Read More

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February 2021

The impact of TLR7 agonist R848 treatment on mast cell phenotype and activity.

Cell Immunol 2021 Jan 28;359:104241. Epub 2020 Oct 28.

Department of Experimental Immunology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland.

Bearing in mind that mast cell contribution to viral clearance is still not fully understood, in this study, we evaluated the effect of Toll-like receptor (TLR)7 viral single-stranded ribonucleic acid (ssRNA) mimic ligand, namely resiquimod (R)848, on mast cell phenotype and activity. We demonstrated that rat peritoneal mast cells exhibit surface and intracellular expression of ssRNA-specific TLR7 molecule, and that mimic ligand switches the self-expression of this receptor. We also detected other proteins associated with the cellular antiviral response: interferon-alpha receptor 1 (IFNAR1), interferon-gamma receptor 1 (IFNGR1), and major histocompatibility complex I (MHC I). Read More

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January 2021

Peptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapy.

Acta Biomater 2020 Oct 2. Epub 2020 Oct 2.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; Helsinki Institute of Life Science (HiLIFE), University of Helsinki, FI-00014 Helsinki, Finland. Electronic address:

Nanomedicines represent innovative and promising alternative technologies to improve the therapeutic effects of different drugs for cancer ablation. Targeting M2-like tumor-associated macrophages (TAMs) has emerged as a favorable therapeutic approach to fight against cancer through the modulation of the tumor microenvironment. However, the immunomodulatory molecules used for this purpose present side effects upon systemic administration, which limits their clinical translation. Read More

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October 2020

Increased nasal mucosal interferon and CCL13 response to a TLR7/8 agonist in asthma and allergic rhinitis.

J Allergy Clin Immunol 2021 Feb 24;147(2):694-703.e12. Epub 2020 Jul 24.

National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:

Background: Acute respiratory viral infections are a major cause of respiratory morbidity and mortality, especially in patients with preexisting lung diseases such as asthma. Toll-like receptors are critical in the early detection of viruses and in activating innate immunity in the respiratory mucosa, but there is no reliable and convenient method by which respiratory mucosal innate immune responses can be measured.

Objective: We sought to assess in vivo immune responses to an innate stimulus and compare responsiveness between healthy volunteers and volunteers with allergy. Read More

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February 2021

High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma.

Sci Adv 2020 Jun 17;6(25):eaba5542. Epub 2020 Jun 17.

Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, USA.

About 40% of patients with non-small cell lung cancer (NSCLC) have stage IV cancer at the time of diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major cause of chemotherapy failure. Read More

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Comparing the immunogenicity of glycosidase-directed resiquimod prodrugs mediated by cancer cell metabolism.

Acta Pharmacol Sin 2020 Jul 25;41(7):995-1004. Epub 2020 May 25.

Department of Chemistry, Washington State University, Pullman, WA, 99164, USA.

We have recently developed an enzyme-directed immunostimulant (EDI) prodrug motif, which is metabolized to active immunostimulant by cancer cells and, following drug efflux, activates nearby immune cells, resulting in immunogenicity. In this study, we synthesized several EDI prodrugs featuring an imidazoquinoline immunostimulant resiquimod (a Toll-like receptor 7/8 agonist) covalently modified with glycosidase enzyme-directing groups selected from substrates of β-glucuronidase, α-mannosidase, or β-galactosidase. We compared the glycosidase-dependent immunogenicity elicited by each EDI in RAW-Blue macrophages following conversion to active immunostimulant by complementary glycosidase. Read More

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Imiquimod suppresses respiratory syncytial virus (RSV) replication via PKA pathway and reduces RSV induced-inflammation and viral load in mice lungs.

Antiviral Res 2020 07 6;179:104817. Epub 2020 May 6.

Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Virología, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Buenos Aires, Argentina. Electronic address:

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and bronchiolitis in children, as well as an important cause of morbidity and mortality in elderly and immunocompromised individuals. However, there is no safe and efficacious RSV vaccine or antiviral treatment. Toll Like Receptors (TLR) are important molecular mediators linking innate and adaptive immunity, and their stimulation by cognate agonists has been explored as antiviral agents. Read More

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Improved protection against Chlamydia muridarum using the native major outer membrane protein trapped in Resiquimod-carrying amphipols and effects in protection with addition of a Th1 (CpG-1826) and a Th2 (Montanide ISA 720) adjuvant.

Vaccine 2020 06 30;38(28):4412-4422. Epub 2020 Apr 30.

Department of Pathology and Laboratory Medicine, Medical Sciences I, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA. Electronic address:

A new vaccine formulated with the Chlamydia muridarum native major outer membrane protein (nMOMP) and amphipols was assessed in an intranasal (i.n.) challenge mouse model. Read More

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Photothermally activatable PDA immune nanomedicine combined with PD-L1 checkpoint blockade for antimetastatic cancer photoimmunotherapy.

J Mater Chem B 2019 04 18;7(15):2499-2511. Epub 2019 Mar 18.

Tianjin Key Laboratory of Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.

Photothermal therapy (PTT) has shown promising potential and bright prospects in damaging primary tumors; however, it is limited to metastatic and recrudescent tumors as PTT requires straightforward light irradiation. Moreover, metastatic and recrudescent tumor immunosuppression due to host T-cell antitumor activity is dramatically impeded because of programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) pathways and immune checkpoint blockade (ICB) therapy. In this work, we demonstrate that PTT combined with ICB could not only eliminate primary tumors, but also prevent tumor metastasis to the lungs/liver. Read More

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Pathogen-Associated Molecular Pattern-Induced TLR2 and TLR4 Activation Increases Keratinocyte Production of Inflammatory Mediators and is Inhibited by Phosphatidylglycerol.

Mol Pharmacol 2020 05 15;97(5):324-335. Epub 2020 Mar 15.

Charlie Norwood VA Medical Center, One Freedom Way, Augusta, Georgia (V.C., W.B.B.); and Departments of Physiology (V.C., S.G., X.C., W.B.B.) and Dermatology (W.B.B.), Medical College of Georgia at Augusta University, Augusta, Georgia

Skin serves not only as a protective barrier to microbial entry into the body but also as an immune organ. The outer layer, the epidermis, is composed predominantly of keratinocytes, which can be stimulated to produce proinflammatory mediators. Although some inflammation is useful to defend against infection, excessive or persistent inflammation can lead to the development of inflammatory skin diseases, such as psoriasis, a common skin disorder affecting approximately 2% of the US population. Read More

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TLR7 Modulated T Cell Response in the Mesenteric Lymph Node of -Infected C57BL/6 Mice.

J Immunol Res 2019 22;2019:2691808. Epub 2019 Dec 22.

The Second Affiliated Hospital, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510260, China.

Toll-like receptors (TLRs) play an important role in regulating immune responses during pathogen infection. However, roles of TLRs on T cells reside in the mesenteric lymph node (MLN) were not be fully elucidated in the course of infection. In this study, T lymphocytes from the mesenteric lymph node (MLN) of -infected mice were isolated and the expression and roles of TLR2, TLR3, TLR4, and TLR7 on both CD4 and CD8 T cells were compared. Read More

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