In vivotargeting of DNA vaccines to dendritic cells using functionalized gold nanoparticles

Gulla, Suresh Kumar ; Rao, Bonda Rama ; Moku, Gopikrishna ; Jinka, Sudhakar ; Nimmu, Narendra Varma ; Khalid, Sara ; Patra, Chitta Ranjan ; Chaudhuri, Arabinda (2019) In vivotargeting of DNA vaccines to dendritic cells using functionalized gold nanoparticles Biomaterials Science, 7 (3). pp. 773-788. ISSN 2047-4830

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Official URL: http://doi.org/10.1039/C8BM01272E

Related URL: http://dx.doi.org/10.1039/C8BM01272E

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.

Item Type:Article
Source:Copyright of this article belongs to Royal Society of Chemistry
ID Code:132005
Deposited On:12 Dec 2022 10:52
Last Modified:12 Dec 2022 10:52

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