Catcher in the rel: Nanoparticles-antibody conjugate as NF-κB nuclear translocation blocker
Journal
Biomaterials
Journal Volume
246
Pages
-
Date Issued
2020
Author(s)
Abstract
Transcription factor complex NF-κB (p65/p50) is localized to the cytoplasm by its inhibitor IκBα. Upon activation, the Rel proteins p65/p50 are released from IκBα and transported through nuclear pore to affect many gene expressions. While inhibitions of up or down stream signal pathways are often ineffective due to crosstalks and compensations, direct blocking of the Rel proteins p65/p50 has long been proposed as a potential target for cancer therapy. In this work, a nanoparticle/antibody complex targeting NF-κB is employed to catch the Rel protein p65 in perinuclear region and thus blocking the translocation near the nuclear pore gate. TAT peptide conjugated on mesoporous silica nanoparticles (MSN) help non-endocytosis cell-membrane transducing and converge toward perinuclear region, where the p65 specific antibody performed the targeting and catching against active NF-κB p65 effectively. The size of the p65 bound nanoparticle becomes too big to enter nucleus. Simultaneous treatment of mice with the hybrid MSN and doxorubicin conferred a significant therapeutic effect against 4T1 tumor-bearing mice. The new approach of anti-body therapy targeting on transcription factor with “nucleus focusing” and “size exclusion blocking” effects of the antibody-conjugated nanoparticle is general and may be applicable to modulating other transcription factors. ? 2020
Subjects
Antibody therapy; Mesoporous silica nanoparticles; NF-κB; Size hindrance; TAT peptide
SDGs
Other Subjects
Antibodies; Cytology; Mammals; Molecular biology; Nanoparticles; Peptides; Silica; Transcription; Transcription factors; Antibody conjugate; Antibody therapy; Mesoporous silica nanoparticles; Nuclear translocations; Perinuclear region; Size hindrance; Tat peptide; Therapeutic effects; Silica nanoparticles; antibody conjugate; antineoplastic agent; doxorubicin; immunoglobulin enhancer binding protein; macrogol; mesoporous silica nanoparticle; nanocarrier; nuclear factor kappa B p65 antibody; protein antibody; transactivator protein; transcription factor RelA; unclassified drug; immunoglobulin enhancer binding protein; nanoparticle; transcription factor RelA; 4T1 cell line; animal cell; animal experiment; animal model; animal tissue; antigen binding; antineoplastic activity; Article; breast cancer; cancer combination chemotherapy; cell nucleus; cellular distribution; concentration response; controlled study; drug delivery system; drug potentiation; drug targeting; endocytosis; mouse; nonhuman; nuclear pore; particle size; priority journal; signal transduction; animal; metabolism; nucleocytoplasmic transport; Active Transport, Cell Nucleus; Animals; Mice; Nanoparticles; NF-kappa B; NF-kappa B p50 Subunit; Signal Transduction; Transcription Factor RelA
Type
journal article