title: Enhancing both CT imaging and natural killer cell-mediated cancer cell killing by a GD2-targeting nanoconstruct.
abstract: Although nanomaterials have been widely investigated for drug delivery, imaging and immunotherapy, their potential roles in triggering innate cellular immune responses while simultaneously serving as imaging enhancer remain unexplored. In this work, gold nanoparticles (GNPs) conjugated to the tumor-targeting anti-GD2 antibody hu14.18K322A, namely HGNPs, were designed and synthesized to specifically enhance computerized tomography (CT) imaging contrast and to stimulate the attack of neuroblastoma and melanoma cells by natural killer (NK) cells. The HGNPs specifically targeted GD2-positive neuroblastoma (NB1691) and melanoma (M21) cells, with an enhancement of CT contrast images of the HGNP-labeled cell pellets by 5.27- and 7.66-fold, respectively, compared to images of unlabeled cell pellets. The HGNPs also triggered NK-mediated antibody-dependent cellular cytotoxicity (ADCC) in NB1691 and M21 cells with a two-fold higher efficacy compared to that elicited by hu14.18K322A alone, with no adverse effect to GD2-negative PC-3 cells. These results suggest that HGNPs are promising theranostic agents for neuroblastoma and melanoma cancers.
authors.affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China; Department of Chemistry, Qilu Normal University, Jinan, Shandong 250013, China.
authors.forename: Peifu
authors.initials: P
authors.lastname: Jiao
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology, Oncology and Bone Marrow Transplant, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Otto
authors.affiliation: Department of Chemistry, Qilu Normal University, Jinan, Shandong 250013, China.
authors.forename: Qiaohong
authors.initials: Q
authors.lastname: Geng
authors.affiliation: TR Pharma & Tech Co., Ltd., Jinan, Shandong 250101, China.
authors.forename: Chencan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Chemistry, Qilu Normal University, Jinan, Shandong 250013, China.
authors.forename: Faming
authors.initials: F
authors.lastname: Li
authors.affiliation: St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Butch
authors.affiliation: St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Snyder
authors.affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhou
authors.affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan