Prussian blue nanoparticle-based antigenicity and adjuvanticity trigger robust antitumor immune responses against neuroblastoma

Biomaterials Science
Juliana Cano-MejiaRohan Fernandes

Abstract

We describe the synthesis of CpG oligodeoxynucleotide-coated Prussian blue nanoparticles (CpG-PBNPs) that function as a nanoimmunotherapy for neuroblastoma, a common childhood cancer. These CpG-PBNPs increase the antigenicity and adjuvanticity of the treated tumors, ultimately driving robust antitumor immunity through a multi-pronged mechanism. CpG-PBNPs are synthesized using a facile layer-by-layer coating scheme resulting in nanoparticles that exhibit monodisperse size distributions and multiday stability without cytotoxicity. The strong intrinsic absorption of PBNPs in the CpG-PBNPs enables ablative photothermal therapy (CpG-PBNP-PTT) that triggers tumor cell death, as well as the release of tumor antigens to increase antigenicity. Simultaneously, the CpG coating functions as an exogenous molecular adjuvant that complements the endogenous adjuvants released by the CpG-PBNP-PTT (e.g. ATP, calreticulin, and HMGB1). In cell culture, coating NPs with CpG increases immunogenicity while maintaining the photothermal activity of PBNPs. When administered in a syngeneic, Neuro2a-based, murine model of neuroblastoma, CpG-PBNP-PTT results in complete tumor regression in a significantly higher proportion (70% at 60 days) of treated anima...Continue Reading

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Citations

May 20, 2020·Frontiers in Immunology·Allan BowenRohan Fernandes
Jan 12, 2021·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Preethi B BalakrishnanRohan Fernandes
Jan 12, 2021·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Michael-Joseph GorbetAshish Ranjan
Jan 26, 2021·Frontiers in Immunology·Shannon J TsaiChristopher M Jewell
Nov 28, 2020·International Journal of Nanomedicine·Peng Xu, Feng Liang
Jan 25, 2020·Molecular Pharmaceutics·Ailton A Sousa-JuniorAndris F Bakuzis
Apr 8, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Yuqian ZhangYang Li

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Methods Mentioned

BETA
dynamic light scattering
irradiating
FACS
flow cytometry

Software Mentioned

VISIONlite
Velox
FlowJo

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