Affiliation: | 1. Applied Biology Division, CSIR-Indian Institute of Chemical Technology (CSIR-IICT) Tarnaka, Uppal Road, Hyderabad, 500 007 India;2. Applied Biology Division, CSIR-Indian Institute of Chemical Technology (CSIR-IICT) Tarnaka, Uppal Road, Hyderabad, 500 007 India
Present address: Telangana Social Welfare Residential Degree College for Women, Bhupalapally 506 168, Telangana, India
These authors contributed equally to this work.;3. Applied Biology Division, CSIR-Indian Institute of Chemical Technology (CSIR-IICT) Tarnaka, Uppal Road, Hyderabad, 500 007 India
These authors contributed equally to this work. |
Abstract: | Herein, we report effective, C-type lectin mannose receptor (MR)-selective, in vivo dendritic cell (DC)-targeting lipid nanoparticles (LNPs) of a novel lipid-containing mannose-mimicking di-shikimoyl- and guanidine head group and two n-hexadecyl hydrophobic tails (DSG). Subcutaneous administration of LNPs of the DSG/p-CMV-GFP complex showed a significant expression of green fluorescence protein in the CD11c+ DCs of the neighboring lymph nodes compared to the control LNPs of the BBG/p-CMV-GFP complex. Mannose receptor-facilitated in vivo DC-targeted vaccination (s.c.) with the electrostatic complex of LNPs of DSG/pCMV-MART1 stimulated long-lasting (270 days post B16F10 tumor challenge) antimelanoma immunity under prophylactic conditions. Remarkably, under therapeutic settings, vaccination (s.c.) with LNPs of the DSG/pCMV-MART1 complex significantly delayed melanoma growth and improved the survival of mice with melanoma. These findings demonstrate that this nonviral delivery system offers a resilient and potential approach to deliver DNA vaccines encoding tumor antigens to DCs in vivo with high efficacy. |