Anti-CD133 Antibody-Targeted Therapeutic Immunomagnetic Albumin Microbeads Loaded with Vincristine-Assisted to Enhance Anti-Glioblastoma Treatment.
Mots clés
Abstrait
Poor tumor cell uptake of anti-tumor drugs is still one of the major challenges for anticancer therapy. Moreover, the deficiency of specific tumor selectivity for tumor sites may further limit the therapeutic effect and cause side effects in healthy regions of the body. Vincristine (VCR) is an effective anti-tumor drug; however, because of its severe nerve toxicity, short half-life, and fast metabolism, its clinical application is limited. Herein, a novel anti-CD133 monoclonal antibody (CD133mAb) targeted therapeutic immunomagnetic albumin microbeads (CD133mAb/TMAMbs) is smartly constructed for enhance anti-glioblastoma treatment, based on specific interaction between cell-membrane antigen CD133 of U251 glioblastoma cells and CD133mAb. Superparamagnetic iron oxide nanoparticles (SPIO NPs) were firstly fabricated as nanocarrier cores, then encapsulated with human serum albumin (HSA) and loaded anti-tumor drug vincristine (VCR), and then CD133mAb, specific affinity with the CD133 expressed on the membrane surface of U251 glioblastoma cells, was subsequently conjugated to form CD133mAb decorated therapeutic immunomagnetic albumin microbeads. The effects of CD133mAb/TMAMbs on the biological behaviors of CD133-overexpressing U251 glioblastoma cells, including proliferation, cell viability, cytoskeletal structure, cell cycle, apoptosis rate, and invasive ability were investigated in detail. The results show that the as-prepared CD133mAb conjugated magnetic albumin microbeads (MAMbs) exhibit a high drug loading capacity, stability and hemocompatibility, and active targeting ability by specific recognition of the CD133 surface antigen by the bioconjugate of CD133mAb. More importantly, the constructed therapeutic CD133mAb/TMAMbs have a specifically effective uptake via the CD133 transmembrane protein that is overexpressed in U251 glioblastoma cells and displayed an effective anti-tumor proliferation and invasive ability. Therefore, based on these results, the fabricated CD133mAb/TMAMbs demonstrate promising uses in brain cancer-targeted diagnosis and therapy.