Anti-CD19 mAb modified mesoporous titanium dioxide as exclusively targeting vector for efficient B-lymphoblastic leukemia therapy

Abstract

B lymphoblastic leukemia (B-LL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mainly occurs in children and adolescents and is one of the main causes of death from malignant tumors in this population. The surface marker CD19 is specifically expressed on the membrane of most malignant B-cells, which is widely used as a marker of B-LL antigen-specific immunotherapy. In this study, mesoporous titanium dioxide nanoparticles (MTNs)-based antibody drug delivery system was designed for B-LL treatment. Anti-CD19 monoclonal antibody was conjugated to PEGylated MTNs, and doxorubicin (DOX) was loaded in the nanoparticle. The CD19-PEG-MTN/DOX nanoparticle could recognize CD19 + B-LL cell lines and induced them apoptosis, but nontoxic for the normal cells. Further, after treated with CD19-PEG-MTN/ DOX nanoparticle, pro-apoptotic proteins Bax and Caspase-3 in KOPN 8 and NALM-6 cells were significantly upregulated, but anti-apoptotic proteins Bcl2, MCL-1, HSP 70, and BAG 3 were downregulated, which indicated the activation of the apoptosis pathway by the nanodrug. By contrast, CD19-PEG-MTN/DOX didn't play a part on CD19 À cell line U937. Besides, the cytotoxicity of CD19-PEG-MTN/DOX was low with good biocompatibility. Collectively, CD19-PEG-MTN/DOX is a promising antitumor nanodrug for the treatment of B-LL.

Nanotechnology-based diagnostics and therapeutics in acute lymphoblastic leukemia: a systematic review of preclinical studies

“…Anti-CD19(Ab) 131,133,195 Targets CD19 overexpressed in B-ALL cells Internalized via endocytosis NL-1 antibody 114 Targets overexpressed CALLA (CD10) in B-ALL cells…”

Antibody‐Incorporated Nanomedicines for Cancer Therapy

“…[559] Furthermore, nanoparticles based on anti-CD19 mAbs have been constructed for the treatment of B-cell lymphoblastic leukemia. [560][561][562] For example, Pan et al designed a DOX delivery system by encapsulating DOX into anti-CD19 mAb-conjugated HSA nanoparticles, and the resultant product was termed DOX/HSA-CD19. [561] In vitro experiments confirmed the effective delivery and strong antiproliferative efficacy of DOX/HSA-CD19 in CD19 + B-lymphoblastic leukemia cell line KOPN-8.…”

Human myogenic progenitor cells display tenogenic differentiation potential and facilitate tendon regeneration

“…The downstream effectors SMAD2 and SMAD3 are able to activate the transcription of tendon-specific genes which further facilitates tendon development and tenogenic differentiation 22,26,27 . After tendon injury, TGFβ/SMAD2/3 promotes the proliferation, migration and differentiation of TDSCs 28 , increases tendon collagen synthesis 29 , and contributes to matrix anabolism for tendon remodeling 30 .…”