Boosting Interleukin ‐12 Antitumor Activity and Synergism with Immunotherapy by Targeted Delivery with isoDGR‐Tagged Nanogold

Gold nanospheres can be functionalized with interleukin ‐12 (IL12), a potent anticancer and immunostimulatory cytokine, and a cyclic peptide containing the isoDGR motif (Iso1) that, after coupling to albumin (Iso1‐HSA), recognizes the αvβ3 integrin overexpressed in tumor vessels and on different tumor cell types. Bifunctional nanospheres (Iso1/Au/I L12) increase the infiltration of immune cells and inhibit tumor growth in preclinical tumor models. AbstractThe clinical use of interleukin ‐12 (IL12), a cytokine endowed with potent immunotherapeutic anticancer activity, is limited by systemic toxicity. The hypothesis is addressed that gold nanoparticles tagged with a tumor‐homing peptide containing isoDGR, an αvβ3‐integrin binding motif, can be exploited for delivering IL12 to tumors and improving its therapeutic index. To this aim, gold nanospheres are functionalized with the head‐to‐tail cyclized‐peptide CGisoDGRG (Iso1) and murine IL12. The resulting nanodrug (Iso1/Au/IL12) is monodispersed, stable, and bifunctional in terms of αvβ3 and IL12‐receptor recogni tion. Low‐dose Iso1/Au/IL12, equivalent to 18–75 pg of IL12, induces antitumor effects in murine models of fibrosarcomas and mammary adenocarcinomas, with no evidence of toxicity. Equivalent doses of Au/IL12 (a nanodrug lacking Iso1) fail to delay tumor growth, whereas 15 000 pg of free IL12 is necessary to achieve similar effects. Iso1/Au/IL12 significantly increases tumor infiltration by inna...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research