Hybrid red blood cell membrane coated porous silicon nanoparticles functionalized with cancer antigen induce depletion of T cells

Rahikkala, Antti; Fontana, Flavia; Bauleth‐Ramos, Tomás; Correia, Alexandra; Kemell, Marianna; Seitsonen, Jani; Mäkilä, Ermei; Sarmento, Bruno; Salonen, Jarno; Ruokolainen, Janne; Hirvonen, Jouni; Santos, Hélder A.

doi:10.1039/d0ra05900e

Cited by 16 publications

(5 citation statements)

References 53 publications

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“…[31][32][33] An example of this is a hybrid NP functionalized with a model cancer antigen, tyrosinase-related protein-2, which was developed to induce the apoptotic cell death of T cells without altering the relative ratio of CD4 þ to CD8 þ T cells in autoimmune diseases. [34] In addition, nano-based strategies can be used to stimulate and maintain long-term immune tolerance in T cells that can restore immune regulatory networks. [35,36] For example, Zhang et al designed a mPEG-PLGA-PLL nanodelivery system to T A B L E 1 Antigen-specific immune tolerance methods.…”

Section: Current Treatmentsmentioning

confidence: 99%

“…Biodegradable PLGA nanoparticles loaded with protein, peptide antigens, epitopes, or rapamycin [26][27][28] Immune system Antigen-specific immune tolerance induction in mice with encephalomyelitis, peanut allergy, or OVAinduced anaphylaxis [15][16][17][18] Promotion of differentiation of naïve T cells into antigen-specific Tregs [13,14,[26][27][28][29][30] Hybrid NP [10,35,36] T cells in autoimmune diseases Induce immune tolerance Hybrid NP functionalized with cancer antigen induces apoptotic cell death in pathogenic T cells without altering the CD4 þ and CD8 þ T cell ratio [16][17][18][19][20]25,[31][32][33][34][35] Nano-delivery transport system [14,37] Immune regulatory networks To simulate and maintain long-term immune tolerance regulatory T cells that can restore immune regulatory networks Transported a Treg-mediated stabilizer (miR-125a) into splenic T cells, thereby correcting the effector and regulatory T cell balance and improving the SLE disease progression transport miR-125a (a stabilizer of Treg-mediated selftolerance with specific effects) into splenic T cells to correct the imbalance of effector/Tregs and significantly inhibit systemic lupus erythematosus (SLE) disease progression. [37] Inorganic NPs, such as gold (Au) and mesoporous silicon (pSi), have been designed to target dendritic cells (DCs) to induce immune tolerance.…”

Section: Silences Sirna In Cells and Skin And Reduces T Cell Activity...mentioning

confidence: 99%

“…Another strategy to induce immune tolerance is to eliminate or suppress pathogenic T cells [31–33] . An example of this is a hybrid NP functionalized with a model cancer antigen, tyrosinase‐related protein‐2, which was developed to induce the apoptotic cell death of T cells without altering the relative ratio of CD4 + to CD8 + T cells in autoimmune diseases [34] . In addition, nano‐based strategies can be used to stimulate and maintain long‐term immune tolerance in T cells that can restore immune regulatory networks [35,36] .…”

Section: Current Treatmentsmentioning

confidence: 99%

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Antigen‐specific mRNA lipid nanoparticle platforms for the prevention and treatment of allergy and autoimmune diseases

Yim,

Zhou,

Yim

et al. 2023

BMEMat

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While most nanomedicines primarily aim to stimulate the immune system against infections or tumors, there is a growing demand for inducing immune tolerance under certain conditions, such as allergic and autoimmune diseases. Researchers have explored nanotechnology‐based strategies to induce immune tolerance in a targeted and specific manner. One approach involves the use of nanoparticles (NPs) to encapsulate immunosuppressive drugs and/or antigens to educate naïve T cells and promote the generation of antigen‐specific regulatory T cells that inhibit immune responses. However, this approach has certain limitations. The hydrophobicity of proteins or peptides restricts the degree to which they can be encapsulated in NPs, which in turn, affects their loading efficiency and treatment efficacy. With the emergence of mRNA lipid nanoparticle (LNP) platforms, there is the possibility of overcoming the limitations of protein and peptide encapsulation. To date, mRNA LNP systems have been shown to provide organ, cellular, and subcellular targeting for the induction of immune tolerance. This method of drug delivery is flexible and scalable that can be customized for a specific patient, resulting in an effective means of administering relevant proteins or epitopes to induce antigen‐specific immune tolerance. With continued research and development, this technology could offer a safer and more effective alternative to current therapies, ultimately improving the quality of life of patients worldwide.

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Section: Current Treatmentsmentioning

confidence: 99%

Section: Silences Sirna In Cells and Skin And Reduces T Cell Activity...mentioning

confidence: 99%

Section: Current Treatmentsmentioning

confidence: 99%

See 1 more Smart Citation

Antigen‐specific mRNA lipid nanoparticle platforms for the prevention and treatment of allergy and autoimmune diseases

Yim,

Zhou,

Yim

et al. 2023

BMEMat

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“…Red blood cell immunity mainly includes identifying and carrying antigen, eliminating circulating immune complexes, enhancing the immune response of T lymphocytes, and promoting the phagocytosis of immune complexes by macrophages. Red blood cells have peroxidase on the surface of their cell membranes, which plays the same killing effect on immune complexes as macrophages [ 5 ]. There are a large number of red blood cells; the number of red blood cells is more than 1,000 times the number of white blood cells.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism Exploration of Autologous Blood Transfusion with RBC Surface Membrane Protein pMHC/aCD28 Combined with CD8+T Cells to Promote the Proliferation of CD8+T Cells to Inhibit the Malignant Transformation of Liver Cancer

Tao

Liu

Yao

et al. 2022

Journal of Oncology

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Autologous blood transfusion is an important blood protection measure. Red blood cells have a certain degree of immunogenicity and their surface membrane proteins CD28 and MHC can participate in the immune response and interact with CD8+ T cells. We build a cell model with a transwell system. The binding characteristics of RBCs and CD8+ T cells were observed with a fluorescent confocal microscope. The content of the inflammatory factor TNF-α and IFN-γ produced was analyzed by ELISA. The proliferation characteristics of CD8+ T cells were analyzed by CFSE staining, and the content of CD3+CD8+ T cells was analyzed by flow cytometry. Cell migration and invasion experiments were used to analyze the malignant metastasis ability of liver cancer cells. The expression of vimentin, E-cadherin, and β-catenin was analyzed by Western blot. We establish a liver cancer model in rats and group them for autologous blood transfusion. The content of CD3+CD8+T cells in the blood of each group of rats was analyzed by flow cytometry. Western blot was used to analyze the expression of vimentin, E-cadherin, and β-catenin in the liver tissues of rats in each group. The red blood cells in the autologous reinfusion blood and CD8+ T cells have an obvious combination. The degree of combination of the two is related to the expression of CD28 and MHC. If CD28 and MHC are expressed at the same time, the combination of the two cells will be high, the proliferation of CD8+ T cells will increase, and the expression of inflammatory factors will also increase, while the expression of the three proteins that are positively correlated with the activity of cancer cells will decrease. If only one of CD28 and MHC is normally expressed, the result is contrary to the situation where both membrane proteins are normally expressed. Our project has proved that autologous infusion of red blood cell surface membrane proteins CD28 and MHC combined with CD8+ T cells can promote the proliferation of CD8+ T cells to inhibit the malignant transformation of liver cancer.

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“…The authors showed that the as-prepared 155Tb loaded SiNPs could be used in targeted radionuclide therapy combined with a chemotherapeutic payload within the porous SiNPs. In another report, Santo's group 142 covalent attachment of a model cancer antigen TRP2, either expressed at the membrane surface or covered by membrane encapsulation, is promising for treating autoimmune diseases by inducing an autoantigen specific immune tolerance.…”

Section: Silicon-based Particles As Drug Delivery Carriersmentioning

confidence: 99%

Silicon-based micro- and nanoparticles: preparation, functionalization and hyperpolarized magnetic resonance imaging

Lin

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of SiNPs and poor size control. The prospect of silicon-based particles as MRI probes with high sensitivity, long relaxation time and excellent polarizability is highly appealing. Therefore, the research described in this thesis aims at promoting the feasibility and versatility of silicon-based particles for hyperpolarized MRI.Specifically, for SiNPs with demonstrated hyperpolarization potential, we improve their stability by surface modification such as polymer grafting or lipid coating (Chapter 3 and Chapter 4), as well as explore available methods for the preparation of non-agglomerated silicon particles (Chapter 5). For silicon carbide, optical pumping has been demonstrated to polarize SiC nuclear spins. [5][6] SiC provides paramagnetic impurities and unpaired electrons that might also be used for hyperpolarization. Besides, both 13 C and 29 Si are MR visible and within the tuning ranges of commercial multinuclear MRI systems. SiC therefore presents an interesting yet hardly explored material for hyperpolarization via DNP. Factors that may affect DNP enhancements and T 1 relaxation times such as crystal structure, size, and chemical composition are under consideration (Chapter 6). The outline of this thesis is as follows:In Chapter 2, a literature review is given, where synthetic strategies and surface modification methods of silicon-based particles are introduced, particularly focusing on silicon particles and silicon carbide. A comprehensive overview of silicon-based particles in hyperpolarization MRI via dynamic nuclear polarization (DNP) is presented, including the basics of the DNP process and mechanism, as well as the physicochemical properties of silicon-based particles that affect DNP performance. In addition, different biomedical applications, including biomedical imaging (fluorescence imaging) and drug delivery with silicon-based nanoparticles are also briefly reviewed. The current limitations and challenges that need to be overcome for successful application of silicon particles in hyperpolarized imaging and multimodal imaging are discussed.

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Hybrid red blood cell membrane coated porous silicon nanoparticles functionalized with cancer antigen induce depletion of T cells

Abstract: We report a study on the effect of red blood cell membrane based cancer antigen-functionalized nanoparticles on peripheral blood T cells. These nanoparticles induce apoptosis of T cells and they may have use in treating autoimmune diseases.

Cited by 16 publications

References 53 publications

Antigen‐specific mRNA lipid nanoparticle platforms for the prevention and treatment of allergy and autoimmune diseases

Antigen‐specific mRNA lipid nanoparticle platforms for the prevention and treatment of allergy and autoimmune diseases

Molecular Mechanism Exploration of Autologous Blood Transfusion with RBC Surface Membrane Protein pMHC/aCD28 Combined with CD8+T Cells to Promote the Proliferation of CD8+T Cells to Inhibit the Malignant Transformation of Liver Cancer

Silicon-based micro- and nanoparticles: preparation, functionalization and hyperpolarized magnetic resonance imaging

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