Main content area

In vivo targeting of DNA vaccines to dendritic cells using functionalized gold nanoparticles

GullaThese authors are contributed equally., Suresh Kumar, Rao, Bonda Rama, Moku, Gopikrishna, Jinka, Sudhakar, NimmuPresent Address: Analytical & Mass Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India., Narendra Varma, Khalid, Sara, Patra, Chitta Ranjan, Chaudhuri, Arabinda
Biomaterials science 2019 v.7 no.3 pp. 773-788
bioactive properties, chemical bonding, dendritic cells, dyes, humans, immune response, immunization, infectious diseases, ligands, lymph nodes, mannose, melanoma, mice, moieties, nanocarriers, nanogold, nanoparticles, near-infrared spectroscopy, physicochemical properties, recombinant vaccines, subcutaneous injection, thiols, transfection
The clinical success of dendritic cell (DC)-based genetic immunization remains critically dependent on the availability of effective and safe nano-carriers for targeting antigen-encoded DNA vaccines to DCs, the most potent antigen-presenting cells in the human body in vivo. Recent studies revealed the efficacies of mannose receptor-mediated in vivo DC-targeted genetic immunization by liposomal DNA vaccine carriers containing both mannose-mimicking shikimoyl and transfection enhancing guanidinyl functionalities. However, to date, the efficacies of this approach have not been examined for metal-based nanoparticle DNA vaccine carriers. Herein, we report for the first time, the design, synthesis, physico-chemical characterization and bioactivities of gold nanoparticles covalently functionalized with a thiol ligand containing both shikimoyl and guanidinyl functionalities (Au-SGSH). We show that Au-SGSH nanoparticles can deliver DNA vaccines to mouse DCs under in vivo conditions. Subcutaneous administration of near infrared (NIR) dye-labeled Au-SGSH showed significant accumulation of the NIR dye in the DCs of the nearby lymph nodes compared to that for the non-targeting NIR-labeled Au-GSH nanoconjugate containing only a covalently tethered guanidinyl group, not the shikimoyl-functionality. Under prophylactic settings, in vivo immunization (s.c.) with the Au-SGSH-pCMV-MART1 nanoplex induced a long-lasting (180 days) immune response against murine melanoma. Notably, mannose receptor-mediated in vivo DC-targeted immunization (s.c.) with the Au-SGSH-MART1 nanoplex significantly inhibited established melanoma growth and increased the overall survivability of melanoma-bearing mice under therapeutic settings. The Au-SGSH nanoparticles reported herein have potential use for in vivo DC-targeted genetic immunization against cancer and infectious diseases.