Activation of human dendritic cells by liposomes derived from total lipid of mycobacterium smegmatis
Liposomes are small-sized, potent, and self-assembled lipids that hold great potential as efficient drug delivery vehicles and adjuvants. They possess a unique vesicular structure and can be derived from natural and synthetic substances. Liposomes can mimic the biological membrane of drugs, thus...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| Online Access: | http://eprints.usm.my/59952/1/NURFATIHAH%20AZLYNA%20BINTI%20AHMAD%20SUHAIMI%20-%20FINAL%20THESIS%20P-UM001119%28R%29%20-D.pdf http://eprints.usm.my/59952/ |
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| Institution: | Universiti Sains Malaysia |
| Language: | English |
| Summary: | Liposomes are small-sized, potent, and self-assembled lipids that hold great
potential as efficient drug delivery vehicles and adjuvants. They possess a unique
vesicular structure and can be derived from natural and synthetic substances.
Liposomes can mimic the biological membrane of drugs, thus extending the half-life
and minimizing the toxicity levels while delivering them to the target organs. The
adjuvant mechanism of liposomes has been intimately associated with the
stimulation of desired immune responses upon the exposure of antigen and immune
cell targeting. This current study mainly targets to investigate the activation of
human DCs by liposomes derived from the total lipid of Mycobacterium smegmatis.
Herein, the liposomes were produced from M. smegmatis total lipid and
characterized under field emission scanning electron microscopy (FESEM),
demonstrating a size ranging from 20 nm-135 nm with spherical structures. The
human whole blood sample was collected and isolated to obtain the peripheral blood
mononuclear cells (PBMCs) from three distinctive groups: TST-negative individuals,
TST-positive individuals, and active pulmonary TB patients. The immune activation
of DCs by M. smegmatis liposomes was analysed by the expression level of DCs
surface markers (HLA-DR, CD11c, CD123, CD86) in flow cytometry and the
secretion of cytokines (IFN-γ, IL-12p70, and IL-4) and via ELISA assay. The
capability of liposomes to improve the antigen presentation during the active state of
TB infection was approved through the increased level of HLA-DR and CD86
alongside the high concentration levels of IL-12p70, IFN-γ, and IL-4 cytokines.
Further confirmation study via FESEM and confocal microscopy recognized the
uptake of M. smegmatis liposomes by DCs. The exposure of liposomes to DCs in all
study groups under FESEM imaging showed the large circular formation on the
surface of DCs which pointed out the presence of liposomes on the surface of DCs
compared to the negative and positive controls. The protrusion of dendrites with
different cell-shaped development with the presence of different stimulators assisted
in the activation of DCs. Similarly, the fluorescence signals observed under the
confocal microscope supported the internalization of liposomes by DCs. Overall, this
study suggests that liposomes have significant potential as effective vaccines and
adjuvants for immunotherapy. |
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