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

Author:
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
Source:
Biomaterials science 2019 v.7 no.3 pp. 773-788
ISSN:
2047-4849
Subject:
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
Abstract:
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.
Agid:
6316227