Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery
Specific delivery to antigen presenting cells (APC) and precise control of the intracellular fate of antigens are crucial to induce cellular immunity that directly and specifically attacks cancer cells. We previously achieved cytoplasmic delivery of antigen and activation of APC using carboxylated c...
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MDPI AG
2020-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/8/754 |
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| author | Eiji Yuba Yoshiki Fukaya Shin Yanagihara Nozomi Kasho Atsushi Harada |
| author_facet | Eiji Yuba Yoshiki Fukaya Shin Yanagihara Nozomi Kasho Atsushi Harada |
| author_sort | Eiji Yuba |
| collection | DOAJ |
| description | Specific delivery to antigen presenting cells (APC) and precise control of the intracellular fate of antigens are crucial to induce cellular immunity that directly and specifically attacks cancer cells. We previously achieved cytoplasmic delivery of antigen and activation of APC using carboxylated curdlan-modified liposomes, which led to the induction of cellular immunity in vivo. APCs express mannose receptors on their surface to recognize pathogen specifically and promote cross-presentation of antigen. In this study, mannose-residue was additionally introduced to carboxylated curdlan as a targeting moiety to APC for further improvement of polysaccharide-based antigen carriers. Mannose-modified curdlan derivatives were synthesized by the condensation between amino group-introduced mannose and carboxy group in pH-sensitive curdlan. Mannose residue-introduced carboxylated curdlan-modified liposomes showed higher pH-sensitivity than that of liposomes modified with conventional carboxylated curdlan. The introduction of mannose-residue to the liposomes induced aggregation in the presence of Concanavalin A, indicating that mannose residues were presented onto liposome surface. Mannose residue-introduced carboxylated curdlan-modified liposomes exhibited high and selective cellular association to APC. Furthermore, mannose residue-introduced carboxylated curdlan-modified liposomes promoted cross-presentation of antigen and induced strong antitumor effects on tumor-bearing mice. Therefore, these liposomes are promising as APC-specific antigen delivery systems for the induction of antigen-specific cellular immunity. |
| first_indexed | 2024-03-10T17:38:21Z |
| format | Article |
| id | doaj.art-2d0b26c4bcbf4366af20b561e8b6215e |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T17:38:21Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2d0b26c4bcbf4366af20b561e8b6215e2023-11-20T09:45:29ZengMDPI AGPharmaceutics1999-49232020-08-0112875410.3390/pharmaceutics12080754Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen DeliveryEiji Yuba0Yoshiki Fukaya1Shin Yanagihara2Nozomi Kasho3Atsushi Harada4Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1–1 Gakuen–cho, Naka–ku, Sakai, Osaka 5998531, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1–1 Gakuen–cho, Naka–ku, Sakai, Osaka 5998531, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1–1 Gakuen–cho, Naka–ku, Sakai, Osaka 5998531, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1–1 Gakuen–cho, Naka–ku, Sakai, Osaka 5998531, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1–1 Gakuen–cho, Naka–ku, Sakai, Osaka 5998531, JapanSpecific delivery to antigen presenting cells (APC) and precise control of the intracellular fate of antigens are crucial to induce cellular immunity that directly and specifically attacks cancer cells. We previously achieved cytoplasmic delivery of antigen and activation of APC using carboxylated curdlan-modified liposomes, which led to the induction of cellular immunity in vivo. APCs express mannose receptors on their surface to recognize pathogen specifically and promote cross-presentation of antigen. In this study, mannose-residue was additionally introduced to carboxylated curdlan as a targeting moiety to APC for further improvement of polysaccharide-based antigen carriers. Mannose-modified curdlan derivatives were synthesized by the condensation between amino group-introduced mannose and carboxy group in pH-sensitive curdlan. Mannose residue-introduced carboxylated curdlan-modified liposomes showed higher pH-sensitivity than that of liposomes modified with conventional carboxylated curdlan. The introduction of mannose-residue to the liposomes induced aggregation in the presence of Concanavalin A, indicating that mannose residues were presented onto liposome surface. Mannose residue-introduced carboxylated curdlan-modified liposomes exhibited high and selective cellular association to APC. Furthermore, mannose residue-introduced carboxylated curdlan-modified liposomes promoted cross-presentation of antigen and induced strong antitumor effects on tumor-bearing mice. Therefore, these liposomes are promising as APC-specific antigen delivery systems for the induction of antigen-specific cellular immunity.https://www.mdpi.com/1999-4923/12/8/754liposomemannosepolysaccharidemacrophagecross-presentationcellular immunity |
| spellingShingle | Eiji Yuba Yoshiki Fukaya Shin Yanagihara Nozomi Kasho Atsushi Harada Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery Pharmaceutics liposome mannose polysaccharide macrophage cross-presentation cellular immunity |
| title | Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery |
| title_full | Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery |
| title_fullStr | Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery |
| title_full_unstemmed | Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery |
| title_short | Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery |
| title_sort | development of mannose modified carboxylated curdlan coated liposomes for antigen presenting cell targeted antigen delivery |
| topic | liposome mannose polysaccharide macrophage cross-presentation cellular immunity |
| url | https://www.mdpi.com/1999-4923/12/8/754 |
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