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Mannose‐Modified Serum Exosomes for the Elevated Uptake to Murine Dendritic Cells and Lymphatic Accumulation
Author(s) -
Choi Eun Seo,
Song Jihyeon,
Kang Yoon Young,
Mok Hyejung
Publication year - 2019
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201900042
Subject(s) - peg ratio , chemistry , mannose , mannose receptor , immune system , dendritic cell , adjuvant , microvesicles , lymph , lymphatic system , in vivo , biophysics , microbiology and biotechnology , immunology , biochemistry , in vitro , biology , medicine , macrophage , microrna , finance , psychiatry , gene , economics
The surface of bovine serum‐derived exosomes (EXOs) are modified with α‐ d ‐mannose for facile interaction with mannose receptors on dendritic cells (DCs) and for efficient delivery of immune stimulators to the DCs. The surface of the EXOs is modified with polyethylene glycol (PEG) without particle aggregation (≈50 nm) via the incorporation of 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine (DSPE) into the lipid layer of the EXO, compared to chemical conjugation by N ‐hydroxysuccinimide activated PEG (NHS‐PEG). PEG modification onto the exosomal surface significantly decreases the non‐specific cellular uptake of the EXOs into the DCs. However, the EXOs with mannose‐conjugated PEG‐DSPE (EXO‐PEG‐man) exhibit excellent intracellular uptake into the DCs and boost the immune response by the incorporation of adjuvant, monophosphoryl lipid A (MPLA) within the EXO. After an intradermal injection, a higher retention of EXO‐PEG‐man is observed in the lymph nodes, which could be used for the efficient delivery of immune stimulators and antigens to the lymph nodes in vivo.