CD19-targeted, Raman tagged gold nanourchins as theranostic agents against acute lymphoblastic leukemia

Abstract

The incidence of Acute Lymphoblastic Leukemia (ALL) is increasing globally, and it is being clinically addressed by chemotherapy, followed by immunotherapy and stem cell transplantation, all with potential life-threatening toxicities. In the need for more effective therapeutics, newly developed disease-targeted nanocompounds can thus hold real potential. In this paper, we propose a novel nanoparticle-based immunotherapeutic agent against ALL, consisting of antiCD19 antibody-conjugated, polyethylene glycol (PEG)-biocompatibilized, and Nile Blue (NB) Raman reporter-tagged gold nanoparticles of urchin-like shape (GNUs), that have a plasmonic response in the Near Infrared (NIR) spectral range. Transmission electron microscopy (TEM) images of particle-incubated CD19-positive (CD19(+)) CCRF-SB cells show that the antiCD19-PEG-NB-GNU nanocomplex is able to recognize the CD19 B-cell-specific antigen, which is a prerequisite for targeted therapy. The therapeutic effect of the particles is confirmed by cell counting, combined with cell cycle analysis by flow cytometry and MTS assay, which additionally offer insights into their mechanisms of action. Specifically, antiCD19-PEG-NB-GNUs proved superior cytotoxic effect against CCRF-SB cells when compared with the free antibody, by reducing the overall viability below 18% after 7 days treatment at a particle-bound antibody concentration of 0.17 ng/μl. Moreover, by combining their remarkable plasmonic properties with the possibility of Raman tagging, the proposed nanoparticles can also serve as spectroscopic imaging agents inside living cells, which validates their theranostic potential in the field of hematological oncology.

Keywords: Acute lymphoblastic leukemia; CD19; Gold nanourchins; Specific targeting; Theranostic agent.