TY - JOUR
T1 - Biocompatible single-chain polymer nanoparticles loaded with an antigen mimetic as potential anticancer vaccine
AU - Gracia, Raquel
AU - Marradi, Marco
AU - Salerno, Gianluca
AU - Pérez-Nicado, Rocmira
AU - Pérez-San Vicente, Adrián
AU - Dupin, Damien
AU - Rodriguez, Javier
AU - Loinaz, Iraida
AU - Chiodo, Fabrizio
AU - Nativi, Cristina
PY - 2018/2/20
Y1 - 2018/2/20
N2 - The "pancarcinoma" Tn antigen (αGalNAc-O-Ser/Thr) is a tumor-associated carbohydrate antigen (TACA) overexpressed on the surface of cancer cells and suitable target for anticancer vaccines. However, TACAs commonly show weak immunogenicity, low in vivo stability, and poor bioavailability. To address these issues, the development of physiologically stable TACA synthetic mimetics and novel nanocarriers for multivalent display are object of intense research. Nanomaterials represent suitable scaffolds to multimerize antigens, but absence of toxicity, easy functionalization and capability to incorporate biomolecules are compulsory characteristics for vaccine nanocarriers. Here, we report on the conjugation of a synthetic Tn-antigen mimetic to biocompatible and water-dispersible dextran-based single-chain nanoparticles (DXT-SCPNs). In vitro stimulation of PBMCs and analysis of interleukins production indicated a specific innate immune modulation mediated by the multivalent presentation of the Tn mimetic at the nanoparticle surface. These preliminary results pave the way for the development of Tn-mimetic clusters on biocompatible DXT-SCPN for TACA-based vaccines.
AB - The "pancarcinoma" Tn antigen (αGalNAc-O-Ser/Thr) is a tumor-associated carbohydrate antigen (TACA) overexpressed on the surface of cancer cells and suitable target for anticancer vaccines. However, TACAs commonly show weak immunogenicity, low in vivo stability, and poor bioavailability. To address these issues, the development of physiologically stable TACA synthetic mimetics and novel nanocarriers for multivalent display are object of intense research. Nanomaterials represent suitable scaffolds to multimerize antigens, but absence of toxicity, easy functionalization and capability to incorporate biomolecules are compulsory characteristics for vaccine nanocarriers. Here, we report on the conjugation of a synthetic Tn-antigen mimetic to biocompatible and water-dispersible dextran-based single-chain nanoparticles (DXT-SCPNs). In vitro stimulation of PBMCs and analysis of interleukins production indicated a specific innate immune modulation mediated by the multivalent presentation of the Tn mimetic at the nanoparticle surface. These preliminary results pave the way for the development of Tn-mimetic clusters on biocompatible DXT-SCPN for TACA-based vaccines.
UR - http://www.scopus.com/inward/record.url?scp=85042368947&partnerID=8YFLogxK
U2 - https://doi.org/10.1021/acsmacrolett.8b00052
DO - https://doi.org/10.1021/acsmacrolett.8b00052
M3 - Article
SN - 2161-1653
VL - 7
SP - 196
EP - 200
JO - ACS MACRO LETTERS
JF - ACS MACRO LETTERS
IS - 2
ER -