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Antigenic Liposomes for Generation of Disease-specific Antibodies
Published on: October 25, 2018
Immunoliposome targeting to CD4+ cells in human blood
1Montreal General Hospital Research Institute, Quebec, Canada.
Insights
Modified liposomes targeting CD4+ cells offer potential for antiviral drug delivery. RES-ve liposomes coated with anti-CD4 antibody effectively target monocytes and lymphocytes, crucial for HIV infection therapies.
Area of Science:
- Nanotechnology
- Immunology
- Pharmacology
Background:
- Liposomes are lipid-based nanoparticles used in drug delivery.
- The reticuloendothelial system (RES) affects liposome circulation time and cellular uptake.
- CD4+ cells, including monocytes and lymphocytes, are primary targets for HIV infection.
Purpose of the Study:
- To investigate the interaction of RES-recognized (RES+ve) and RES-unrecognized (RES-ve) liposomes with CD4+ cells.
- To determine if surface modification of RES-ve liposomes can enable targeted delivery to CD4+ cells.
- To evaluate the potential of these targeted liposomes for antiviral therapy, particularly against HIV.
Main Methods:
- Preparation of RES+ve and RES-ve liposomes from different phospholipid formulations.
- Incubation of liposomes with purified leukocyte fractions and whole blood to assess binding to monocytes and lymphocytes.
- Surface functionalization of RES-ve liposomes with anti-Leu3A (CD4) monoclonal antibody.
- In vivo pharmacokinetic studies in mice to determine liposome circulation half-life.
- Blocking studies using free anti-Leu3A antibody to confirm specific binding.
Main Results:
- RES+ve liposomes bound to monocytes but not lymphocytes.
- RES-ve liposomes showed no significant binding to either monocytes or lymphocytes.
- Anti-CD4 antibody-conjugated RES-ve liposomes effectively bound to both monocytes and lymphocytes.
- This specific binding was confirmed by blocking experiments with free anti-CD4 antibody.
- RES-ve liposomes exhibited prolonged circulation in mice (half-life > 5 hours) compared to RES+ve liposomes.
Conclusions:
- RES-ve liposomes can be engineered for targeted delivery to CD4+ cells by surface functionalization with anti-CD4 antibodies.
- This targeted liposome approach shows promise for delivering antiviral agents to cells susceptible to HIV infection.
- The prolonged circulation of RES-ve liposomes enhances their potential as a drug delivery vehicle for chronic conditions like HIV.
Abstract:
Liposomes were prepared from phospholipid formulations recognized or ignored by cells of the reticuloendothelial system (RES+ve or RES-ve, respectively). The ability of these liposomes to interact with CD4+ve cells in purified leukocyte fractions or in whole blood has been determined. RES+ve liposomes bound to monocytes in purified leukocyte fractions or in whole blood, but did not bind to lymphocytes. RES-ve liposomes did not bind to either monocytes or lymphocytes. The attachment of an anti-Leu3A (CD4) monoclonal antibody to the outer surface of RES-ve liposomes resulted in their interaction with both monocytes and lymphocytes. The binding was blocked by prior incubation of the leukocytes with free anti-Leu3A antibody. RES+ve liposomes were rapidly eliminated from the circulation of mice after intravenous injection, whereas RES-ve liposomes remained in the circulation for prolonged periods of time (half-life much greater than 5 h), even after incubation with the opsinizing acute-phase reactant, C-reactive protein. These results suggest that RES-ve liposomes possessing surface-bound anti-Leu3A may provide a means of targeting antiviral agents to those cells at risk from HIV infection.
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