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Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy
Author(s) -
Yi Sijia,
Zhang Xiaohan,
Sangji M. Hussain,
Liu Yugang,
Allen Sean D.,
Xiao Baixue,
Bobbala Sharan,
Braverman Cameron L.,
Cai Lei,
Hecker Peter I.,
DeBerge Matthew,
Thorp Edward B.,
Temel Ryan E.,
Stupp Samuel I.,
Scott Evan A.
Publication year - 2019
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201904399
Subject(s) - polymersome , nanocarriers , inflammation , materials science , dendritic cell , ethylene glycol , cancer research , cd11c , pharmacology , immunology , microbiology and biotechnology , biophysics , immune system , medicine , drug delivery , chemistry , nanotechnology , biology , biochemistry , phenotype , composite material , copolymer , amphiphile , polymer , organic chemistry , gene
The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro‐inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T‐cell (Treg) activation. Here, the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)‐ b ‐poly(propylene sulfide) copolymers to enhance the targeted modulation of DCs by transporting the anti‐inflammatory agent 1,25‐dihydroxyvitamin D3‐(aVD) and ApoB‐100‐derived antigenic peptide P210 are engineered. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P‐D2 peptide, which binds CD11c on the DC surface, significantly enhance the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Weekly low‐dose intravenous administration of DC‐targeted, aVD‐loaded polymersomes significantly inhibit atherosclerotic lesion development in high‐fat‐diet‐fed ApoE −/− mice. The results validate the key role of DC immunomodulation during aVD‐dependent inhibition of atherosclerosis and demonstrate the therapeutic enhancement and dosage lowering capability of cell‐targeted nanotherapy in the treatment of CVD.