70-kDa heat shock protein coated magnetic nanocarriers as a nanovaccine for induction of anti-tumor immune response in experimental glioma.

作者: Maxim A. Shevtsov , Boris P. Nikolaev , Liudmila Y. Yakovleva , Marina A. Parr , Yaroslav Y. Marchenko

DOI: 10.1016/J.JCONREL.2015.10.051

关键词:

摘要: Nanovaccines based on superparamagnetic iron oxide nanoparticles (SPIONs) provide a novel approach to induce the humoral and cell-based immune system fight cancer. Herein, we increased immunostimulatory capacity of SPIONs by coating them with recombinant heat shock protein 70 (Hsp70) which is known chaperone antigenic peptides. After binding, Hsp70-SPIONs deliver immunogenic peptides from tumor lysates dendritiс cells (DCs) thus stimulate tumor-specific, CD8+ cytotoxic T cell response. We could show that binding activity substrate-binding domain (SBD) highly dependent ATPase its nucleotide-binding NBD), as shown (31)P NMR spectroscopy. Immunization C6 glioma-bearing rats DCs pulsed resulted in delayed progression (as measured MRI) an overall survival. In parallel IFNγ secretion were detected serum these animals immunohistological analysis subsequent cryosections glioma revealed enhanced infiltration memory CD45RO+ cells. Taken together study demonstrates magnetic nanocarriers such coated Hsp70 can be applied platform for boosting anti-cancer responses.

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