Article ; Online: Sialic acid-conjugate modified doxorubicin nanoplatform for treating neutrophil-related inflammation.
Journal of controlled release : official journal of the Controlled Release Society
2021 Volume 337, Page(s) 612–627
Abstract: ... disease-19 (COVID-19), sepsis, etc. Herein, we used sialic acid-modified liposomal doxorubicin (DOX-SAL ... on inflammatory neutrophil membranes. In inflammation models of acute lung inflammation/injury (ALI), sepsis, and ... of inflammatory neutrophils, enabling specific inhibition of the core disease process and the potential to treat ...
| Abstract | Neutrophils, the most abundant leukocytes in human peripheral blood, are important effector cells that mediate the inflammatory response. During neutrophil dysfunction, excessive activation and uncontrolled infiltration are the core processes in the progression of inflammation-related diseases, including severe coronavirus disease-19 (COVID-19), sepsis, etc. Herein, we used sialic acid-modified liposomal doxorubicin (DOX-SAL) to selectively target inflammatory neutrophils in the peripheral blood and deliver DOX intracellularly, inducing neutrophil apoptosis, blocking neutrophil migration, and inhibiting the inflammatory response. Strong selectivity resulted from the specific affinity between SA and L-selectin, which is highly expressed on inflammatory neutrophil membranes. In inflammation models of acute lung inflammation/injury (ALI), sepsis, and rheumatoid arthritis (RA), DOX-SAL suppressed the inflammatory response, increased the survival of mice, and delayed disease progression, respectively. Moreover, DOX-SAL restored immune homeostasis in the body, without side effects. We have presented a targeted nanocarrier drug delivery system that can block the recruitment of inflammatory neutrophils, enabling specific inhibition of the core disease process and the potential to treat multiple diseases with a single drug. This represents a revolutionary treatment strategy for inflammatory diseases caused by inappropriate neutrophil activation. |
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| MeSH term(s) | Animals ; COVID-19 ; Doxorubicin ; Humans ; Inflammation/drug therapy ; Mice ; N-Acetylneuraminic Acid ; Neutrophils ; SARS-CoV-2 |
| Chemical Substances | Doxorubicin (80168379AG) ; N-Acetylneuraminic Acid (GZP2782OP0) |
| Language | English |
| Publishing date | 2021-07-28 |
| Publishing country | Netherlands |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 632533-6 |
| ISSN | 1873-4995 ; 0168-3659 |
| ISSN (online) | 1873-4995 |
| ISSN | 0168-3659 |
| DOI | 10.1016/j.jconrel.2021.07.044 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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