DNA-BASED HYBRID LIQUID CRYSTALLINE NANO ORGANOMETALLIC COMPOSITES FOR TARGETED DRUG DELIVERY IN NEUTRON CAPTURE THERAPY

摘要

Objective: The aim of this work was focused on the obtaining a DNA-based hybrid nano liquid crystalline organometallic composites for targeted drug delivery in neutron capture therapy. Methods: The formation of a cholesteric liquid crystalline DNA (CLCD-DNA) dispersion has performed using ultrasonic depolymerized calf thymus DNA(MW-0.6-0.8×10 6 Da)2×10 -7 M, mixing with polyethylene glycol8.5×10 -5 M, dissolved in the 0.3 M NaCl solution and incubated over 1,0 h at 20 °C. CLCD-DNA formation process was determined and controlled by measuring absorption value of circular dichroism (CD) spectrum in the range of 350-600 nm. The organometallic DNA-Gd compound was formed by processing the obtained CLCD-DNA with 2.49 × 10 -4 M, 4.97 × 10 -4 M, 9.8 × 10 -4 M, 1.48× 10 -3 M, 2.92 × 10 -3 M GdCl 3 aqueous solutions. CLCD-DNA-gadolinium complex formation process was registered over the appearance of 2 nd amplitude in the CD spectrum. DNA-Gd complex dispersion toxicity was evaluated over 40 min, 24h and 72h incubation with 1×10 6 cells in the RPMI-40 medium supplemented with 3×10 -4 M Gd 3+ . Results: The obtained CLCD-DNA-Gd (d~500 nm) particles was shown less toxicity and higher viability percentage of macrophages after 40 min incubation with CLCD-DNA-Gd contains Gd 3+ ions concentration 3×10 -4 M showed 100% viability and after 72 h ours approximately 89%. The cells immobilized with CLCD-DNA-Gd particles contains 3×10 -4 M Gd 3+ , neutron irritation was caused a 100% cell deaths. Conclusion: Obtained relatively stable, non-cytotoxic drug forms with a maximum local concentration of gadolinium (400 μg/ml). The effectiveness of these nanosystems for targeted drug delivery has markedly superior efficacy than 10 B and other products were based on gadolinium.