Plga immunosuppressant

Dendritic cells (DCs) are the most potent antigen-presenting cells that have multifaceted functions in the control of immune activation and tolerance. Hyperresponsiveness and altered tolerogenicity of DCs contribute to the development and pathogenesis of system lupus erythematosus (SLE); therefore, DC-targeted therapies aimed at inducing specific immune tolerance have become of great importance for the treatment of SLE. This study developed a new nanoparticle (NP) containing a biodegradable PDMAEMA-PLGA copolymer for target-oriented delivery to DCs in situ...

Inflammatory cells mount an immune response against in vitro engineered cartilage implanted into immunocompetent animals, consequently limiting the usage of tissue-engineered cartilage to repair cartilage defects. In this study, curcumin (Cur)-an anti-inflammatory agent-was mixed with poly(lactic-co-glycolic acid) (PLGA) to develop a Cur/PLGA nanofibrous membrane with nanoscale pore size and anti-inflammatory properties. Fourier-transform infrared spectroscopy and high-performance liquid chromatography analyses confirmed the successful loading of Cur into the Cur/PLGA nanofibrous membrane...

Despite current developments in bone substitute technology for spinal fusion, there is a lack of adequate materials for bone regeneration in clinical applications. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is commercially available, but a severe inflammatory response is a known side effect. Bone graft substitutes that enhance osteogenesis without adverse effects are needed. We developed a bioactive molecule-laden PLGA composite with multi-modulation for bone fusion. This bioresorbable composite scaffold was considered for bone tissue engineering...

Innovative Pickering emulsions co-encapsulating two active pharmaceutical ingredients (API) were formulated for a topical use. An immunosuppressive agent, either cyclosporine A (CysA) or tacrolimus (TAC), was encapsulated at high drug loading in biodegradable and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). These NP stabilized the oil droplets (Miglyol) containing an anti-inflammatory drug, calcitriol (CAL). The influence of the API on the physico-chemical properties of these emulsions were studied...

Tumour-associated macrophages (TAMs) often promote cancer progression through immunosuppression in the tumour microenvironment (TME). However, the signalling pathways crosstalk responsible for this mechanism remain unclear. The aim of our study was to investigate whether the interaction between TAMs and colorectal cancer cells could be down-regulated by nanoparticles (NPs) loaded with retinoic acid (RA) and coated with cholesterol (CHO), in combination with an anti-PD-L1 immune checkpoint inhibitor. Tumours were evaluated by qRT-PCR and immunohistochemistry from allographic tumour growth model...

Oral immunosuppressant methotrexate (MTX) is an effective method for the treatment of inflammatory bowel disease (IBD). To overcome the defects of clinical application of MTX, poly (lactic-co-glycolic acid) (PLGA), Eudragits® S100 (ES100), chitosan (CS) and hyaluronic acid (HA) were used to structure the MTX-loaded HA-CS/ES100/PLGA nanoparticles (MTX@hCEP). MTX@hCEP had a hydrodynamic particle size of approximately 202.5 nm, narrow size distribution, negative zeta potential (-18.7 mV), and smooth surface morphology...

Antitumor immunotherapy has become a powerful therapeutic modality to identify and kill various malignant tumors by harnessing the immune system. However, it is hampered by the immunosuppressive microenvironment and poor immunogenicity in malignant tumors. Herein, in order to achieve multi-loading of drugs with different pharmacokinetic properties and targets, a charge reversal yolk-shell liposome co-loaded with JQ1 and doxorubicin (DOX) into the PLGA yolk and the lumen of the liposome respectively was engineered to increase hydrophobic drug loading capacity and stability under physiological conditions and further enhance tumor chemotherapy via blockade programmed death ligand 1 (PD-L1) pathway...

Immunotherapy has had a profound positive effect on certain types of cancer but has not improved the outcomes of glioma because of the blood-brain barrier (BBB) and immunosuppressive tumor microenvironment. In this study, we developed an activated mature dendritic cell membrane (aDCM)-coated nanoplatform, rapamycin (RAPA)-loaded poly(lactic- co -glycolic acid) (PLGA), named aDCM@PLGA/RAPA, which is a simple, efficient, and individualized strategy to cross the BBB and improve the immune microenvironment precisely...

Although immunotherapy has revolutionized oncotherapy, only ≈15% of head and neck squamous cell carcinoma (HNSCC) patients benefit from the current therapies. An immunosuppressive tumor microenvironment (TME) and dysregulation of the polycomb ring finger oncogene BMI1 are potential reasons for the failure. Herein, to promote immunotherapeutic efficacy against HNSCC, an injectable nanocomposite hydrogel is developed with a polymer framework (PLGA-PEG-PLGA) that is loaded with both imiquimod encapsulated CaCO3 nanoparticles (RC) and cancer cell membrane (CCM)-coated mesoporous silica nanoparticles containing a peptide-based proteolysis-targeting chimeras (PROTAC) for BMI1 and paclitaxel (PepM@PacC)...

Autoimmune diseases affect over 4% of the world's population. Treatments are generally palliative or use broad spectrum immunosuppressants to reduce symptoms and disease progression. In some diseases, antibodies generated to a single autoantigen are the major cause of pathogenic inflammation, suggesting that treatments to induce tolerance to the autoantigen could be therapeutic. Here we report the development of hybrid nanoparticles (NPs) that induce tolerance in both T cells and B cells. The NPs comprise a lipid monolayer encapsulating a PLGA core loaded with rapamycin that promotes development of regulatory T cells (Tregs)...

To improve radiotherapy effect by inducing more toxicity for tumors and less for normal tissue and switching immunosuppressive microenvironment caused by expression of PD-L1 and tumor-associated macrophages (TAMs) to immunoreactive microenvironment, we designed a PD-L1-targeted nanoplatform consisting of gold nanoparticles and superparamagnetic iron oxide nanoparticles (antiPD-L1-SPIOs@PLGA@Au). In vivo T2-weighted images, the best contrast effect of tumor was achieved two hours after intravenous injection of antiPD-L1-SPIOs@PLGA@Au...

Studies show that infiltrated myeloid-derived suppressor cells (MDSCs) are vital in the immunosuppressive tumor microenvironment and account for lymphoma refractoriness and recurrence. Here, we developed a biomimetic nanoplatform (PM-PLGA-DOX/GEM) in which platelet membranes (PM) wrap PLGA nanoparticles co-loaded with doxorubicin (DOX) and gemcitabine (GEM). PM-PLGA-DOX/GEM would accumulate in tumor tissues because of the enhanced permeation and retention (EPR) effect and the tumor cell-induced platelet aggregation (TCIPA) effect...

Patients with high-risk non-metastatic renal cell carcinoma (RCC) are at risk of metastatic relapse following nephrectomy. Cabozantinib (CZ), a potent multitarget tyrosine kinase inhibitor, interferes with angiogenesis and immunosuppression associated with surgery-induced metastasis. Here, we explored the therapeutic potential of CZ-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CZ-PLGA-NPs) as an adjuvant strategy for targeting post-nephrectomy metastasis. A clinically relevant subline recapitulating post-nephrectomy lung metastasis of high-risk human RCC, namely Renca-SRLu5-Luc, was established through in vivo serial selection of luciferase-expressing murine RCC Renca-Luc cells...

Antigen-specific therapies hold promise for treating autoimmune diseases such as multiple sclerosis while avoiding the deleterious side effects of systemic immune suppression due to delivering the disease-specific antigen as part of the treatment. In this study, an antigen-specific dual-sized microparticle (dMP) treatment reversed hind limb paralysis when administered in mice with advanced experimental autoimmune encephalomyelitis (EAE). Treatment reduced central nervous system (CNS) immune cell infiltration, demyelination, and inflammatory cytokine levels...

The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthermore, for highly malignant tumors, simply enhancing ICD is insufficient for exhaustively eliminating the tumor and inhibiting metastasis. Herein, we propose a unique magnetothermal-dynamic immunotherapy strategy based on liquid-solid transformation porous versatile implants (Fe3 O4 /AIPH@PLGA) that takes advantage of less energy loss and avoids ongoing circulating losses by minimally invasive injection into tumors...

Glioblastoma (GBM), the most common subtype of malignant gliomas, is characterized by aggressive infiltration, high malignancy, and poor prognosis. The frustrating anti-GBM outcome of conventional therapeutics is due to the immunosuppressive milieu, in addition to the formidable obstacle of the blood-brain barrier (BBB). Combination therapy with an immune checkpoint blockade (ICB) has emerged as a critical component in the treatment of GBM. Here, we report an engineered macrophage-membrane-coated nanoplatform with enhanced programmed cell death-1 (PD-1) expression (PD-1-MM@PLGA/RAPA)...

Chemotherapy promotes phosphatidylserine (PS) externalization in tumors undergoing apoptosis, forms an immunosuppressive tumor microenvironment (TME), and inhibits dendritic cell (DC) maturation and antigen presentation by binding PS receptors expressed in DCs, thereby limiting naive T cell education and activation. In this study, we demonstrate a selective nanocarrier system composed of annexin A5-labeled poly (lactide-co-glycolide) nanoparticles (PLGA_NPs) encapsulating tumor specific antigen or neoantigen, to target apoptotic tumor cells expressing PS as an innate immune checkpoint inhibitor (ICI) that induces active cancer immunotherapy...

Current therapeutic strategies for autoimmune diseases such as multiple sclerosis (MS) are directed towards nonspecific immunosuppression, which has severe side effects. The induction of antigen-specific tolerance has become an ideal therapy for autoimmune diseases. In this study, we have constructed a dual peptide nanoparticle platform, including the antigen peptide of the primary signal and inhibitory peptide of the co-stimulatory signal, for T-cell activation and to trigger antigen-specific immune tolerance to treat experimental autoimmune encephalomyelitis (EAE), a murine model for MS...

Hepatocellular carcinoma (HCC) is resistant to current immunotherapy. This poor outcome mainly results from the immunosuppressive characteristics of tumor microenvironment (TME). Accumulating evidence indicates that some chemotherapy agents trigger immunogenic cell death (ICD), providing a promising strategy to remodel the immunosuppressive TME. The role of Plumbagin (PLB, a naphthoquinone compound from Plumbago zeylanica L.) as the ICD inducer for HCC cells was confirmed in this study. Dihydrotanshinone I (DIH, a phenanthraquinone compound of Salvia miltiorrhiza) functioned as the ICD enhancer by generating the reactive oxygen species (ROS)...

Purpose: Mesangial cells-mediated glomerulonephritis refers to a category of immunologically mediated glomerular injuries characterized by infiltration of circulating inflammatory cells, proliferation of mesangial cells, and the common pathological manifestation to the later stage is renal fibrosis, accompanied by excessive accumulation of extracellular matrix (ECM). Treatment regimens include glucocorticoids and immunosuppressive agents, but their off-target distribution causes severe systemic toxicity...