Dendritic cell-targeted liposomes for cancer immunotherapy via inhibition of aryl hydrocarbon receptor

Area of Science:

• Immunology
• Cancer Biology
• Nanomedicine

Background:

• Aryl hydrocarbon receptor (AhR) ligands, like kynurenine, are immunosuppressive in the tumor microenvironment.
• Systemic AhR inhibition shows antitumor effects, but targeting AhR specifically in dendritic cells (DCs) is not well understood.

Purpose of the Study:

• To investigate the effects of targeting AhR in DCs for cancer immunotherapy.
• To develop a DC-targeted drug delivery system for an AhR inhibitor.

Main Methods:

• Phage display identified a DC-specific peptide (SP65) targeting CD11c.
• SP65-functionalized liposomes (SP65-lipo-CH) delivered the AhR inhibitor CH223191 to DCs.
• Assessed IL-12 secretion in DCs and IFN-γ production and tumor-killing activity in NK cells.
• Evaluated tumor suppression and survival in MC38 and LLC mouse models.

Main Results:

• SP65-functionalized liposomes demonstrated enhanced drug uptake and selectivity for DCs.
• SP65-lipo-CH treatment promoted IL-12 secretion in DCs.
• Co-culture with SP65-lipo-CH-treated DCs increased NK cell IFN-γ production and tumor-killing capacity.
• SP65-lipo-CH alone suppressed tumor growth and prolonged survival in mouse models.

Conclusions:

• SP65-lipo-CH effectively targets DCs to modulate innate immunity via AhR inhibition.
• This approach enhances DC and NK cell function, representing a promising strategy for cancer immunotherapy.