Comparative evaluation of cell- and serum-derived exosomes to deliver immune stimulators to lymph nodes

Yu, Gyeonghui; Jung, Heesun; Kang, Yoon Young; Mok, Hyejung

doi:10.1016/j.biomaterials.2018.02.003

Biomaterials

2018

DOI: 10.1016/j.biomaterials.2018.02.003

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Comparative evaluation of cell- and serum-derived exosomes to deliver immune stimulators to lymph nodes

Gyeonghui Yu

Heesun Jung

Yoon Young Kang

et al.

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Cited by 40 publications

(41 citation statements)

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“…In previous studies, melanoma antigen peptide TRP2 was incorporated into polymeric nanoparticles, inorganic nanoparticles, and liposomes and then delivered into lymph nodes for antitumor immunity . In the present study, serum‐derived EXOs were utilized for the delivery of peptide antigen TRP2 into lymph nodes.…”

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confidence: 95%

“…As a result, it may be beneficial to develop carrier systems for delivering peptide antigens to immune cells . To improve the biological performance of peptide antigens as cancer vaccines, biomaterials such as nanoparticles, microparticles, and hydrogels have been used to encapsulate peptides . In particular, nanosized particles have been designed that can deliver antigens and immune stimulators to lymph nodes .…”

mentioning

confidence: 99%

“…The antigens on the surface of APCs were then able to activate CD8+ cytotoxic T cells, which can mediate selective antitumor immune responses . To boost the immune response, adjuvant molecules such as monophosphoryl lipid A (MPLA) were incorporated into the nanoparticles and delivered along with antigens . The targeted and efficient accumulation of antigens and immune stimulators in lymph nodes is considered a crucial factor for boosting the immune response …”

mentioning

confidence: 99%

“…To ensure successful localization of biomaterials to lymph nodes, the physicochemical properties of the particles, such as the hydrodynamic size and surface charge, should be considered . For example, particles of size 10–100 nm are able to penetrate lymphatic capillaries and accumulate in the lymph nodes, whereas particles below 6 nm tend to drain into the blood vessels .…”

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confidence: 99%

“…There have been only a few reports of using cell‐derived EXOs to deliver antigen peptides . In our previous studies, serum‐derived EXOs exhibited a number of improved properties over cell‐derived EXOs, such as lymph node accumulation, which is important for immune stimulation . In particular, the uniform size distribution of serum‐derived EXOs (below 50 nm) allows for superior lymphatic accumulation after intradermal injection.…”

mentioning

confidence: 99%

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Efficient Delivery of Tyrosinase Related Protein‐2 (TRP2) Peptides to Lymph Nodes using Serum‐Derived Exosomes

Park

Choi

et al. 2018

Macromolecular Bioscience

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Exosomes (EXO) are considered to be versatile carriers for biomolecules; however, the delivery of therapeutic peptides using EXOs poses several challenges. In this study, the efficiency of serum‐derived EXOs in delivering tyrosinase‐related protein‐2 (TRP2) peptides to lymph nodes is determined. TRP2 peptides are successfully incorporated into EXOs, which show a uniform and narrow size distribution of around 45 nm. The TRP2‐incorporated exosomes (EXO‐TRP2) are efficiently internalized into macrophages and dendritic cells, and are seen to display a punctate distribution. EXOs loaded with TRP2 together with MPLA, (EXO‐MPLA‐TRP2) result in a strong release of proinflammatory cytokines (TNF‐α and IL‐6) from both RAW264.7 and DC2.4 cells. Finally, subcutaneous injection of fluorescently labeled EXO‐TRP2 followed by ex vivo imaging using in vivo imaging system (IVIS) show a strong fluorescent signal in the lymph nodes after only 1 h, which is maintained until at least 4 h after injection. Taken together, the findings suggest that serum‐derived EXOs can serve as promising carriers to deliver therapeutic peptides to lymph nodes for immunotherapy.

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confidence: 95%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Efficient Delivery of Tyrosinase Related Protein‐2 (TRP2) Peptides to Lymph Nodes using Serum‐Derived Exosomes

Park

Choi

et al. 2018

Macromolecular Bioscience

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Nanovesicle‐Mediated Targeted Delivery of Immune Checkpoint Blockades to Potentiate Therapeutic Efficacy and Prevent Side Effects

et al. 2022

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Despite the clinically proven efficacies of immune checkpoint blockades, including anti‐cytotoxic T lymphocyte‐associated protein 4 antibody (αCTLA‐4), the low response rate and immune‐related adverse events (irAEs) in cancer patients represent major drawbacks of the therapy. These drawbacks of αCTLA‐4 therapy are mainly due to the suboptimal activation of tumor‐specific cytotoxic T lymphocytes (CTLs) and the systemic nonspecific activation of T cells. To overcome such drawbacks, αCTLA‐4 is delivered by dendritic cell‐derived nanovesicles presenting tumor antigens (DCNV‐TAs) that exclusively interact with tumor‐specific T cells, leading to selective activation of tumor‐specific CTLs. Compared to conventional αCTLA‐4 therapy, treatment with αCTLA‐4‐conjugated DCNV‐TAs significantly inhibits tumor growth and reduces irAEs in syngeneic tumor‐bearing mice. This study demonstrates that the spatiotemporal presentation of both αCTLA‐4 and tumor antigens enables selective activation of tumor‐specific T cells and potentiates the antitumor efficacy of αCTLA‐4 without inducing systemic irAEs.

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Chemically Engineered Immune Cell‐Derived Microrobots and Biomimetic Nanoparticles: Emerging Biodiagnostic and Therapeutic Tools

et al. 2021

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Over the past decades, considerable attention has been dedicated to the exploitation of diverse immune cells as therapeutic and/or diagnostic cell-based microrobots for hard-to-treat disorders. To date, a plethora of therapeutics based on alive immune cells, surface-engineered immune cells, immunocytes' cell membranes, leukocyte-derived extracellular vesicles or exosomes, and artificial immune cells have been investigated and a few have been introduced into the market. These systems take advantage of the unique characteristics and functions of immune cells, including their presence in circulating blood and various tissues, complex crosstalk properties, high affinity to different self and foreign markers, unique potential of their on-demand navigation and activity, production of a variety of chemokines/cytokines, as well as being cytotoxic in particular conditions. Here, the latest progress in the development of engineered therapeutics and diagnostics inspired by immune cells to ameliorate cancer, inflammatory conditions, autoimmune diseases, neurodegenerative disorders, cardiovascular complications, and infectious diseases is reviewed, and finally, the perspective for their clinical application is delineated.

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Comparative evaluation of cell- and serum-derived exosomes to deliver immune stimulators to lymph nodes

Cited by 40 publications

References 51 publications

Efficient Delivery of Tyrosinase Related Protein‐2 (TRP2) Peptides to Lymph Nodes using Serum‐Derived Exosomes

Efficient Delivery of Tyrosinase Related Protein‐2 (TRP2) Peptides to Lymph Nodes using Serum‐Derived Exosomes

Nanovesicle‐Mediated Targeted Delivery of Immune Checkpoint Blockades to Potentiate Therapeutic Efficacy and Prevent Side Effects

Chemically Engineered Immune Cell‐Derived Microrobots and Biomimetic Nanoparticles: Emerging Biodiagnostic and Therapeutic Tools

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