99m Tc-doxorubicin-loaded gallic acid-gold nanoparticles ( 99m Tc-DOX-loaded GA-Au NPs) as a multifunctional theranostic agent

• Published in: International journal of pharmaceutics 2020-08, Vol.586, p.119514
• Main Authors: El-Ghareb, Walaa I, Swidan, Mohamed M, Ibrahim, Ismail T, Abd El-Bary, Ahmed, Tadros, Mina Ibrahim, Sakr, Tamer M
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacology; Breast Neoplasms - drug therapy; Cell Line, Tumor; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Delivery Systems; Female; Gallic Acid - chemistry; Gold - chemistry; Humans; Inhibitory Concentration 50; MCF-7 Cells; Metal Nanoparticles; Mice; Particle Size; Precision Medicine; Technetium - chemistry
• ISSN: 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119514

The development of cancer theranostic nanomedicines is recommended to concurrently achieve and evaluate the therapeutic benefit and progress. The current work aims to develop gallic acid-gold nanoparticles (GA-Au NPs) as a theranostic probe for Tc-Doxorubicin ( Tc-DOX) based on the spatiotemporal release pattern induced intra-tumoral (IT) delivery. DOX-loaded GA-Au NPs were developed and identified via UV-Vis spectroscopy. The system was characterized for drug loading efficiency%, particle size, zeta potential, topography, in vitro DOX release and anti-proliferative activity against the MCF-7 cell-line. The factors influencing radiolabeling efficiency of DOX with Tc (DOX concentration, stannous chloride concentration, reaction time and pH) were optimized. The in vitro stability in mice serum and in vivo distribution studies in mice of Tc-DOX-loaded GA-Au NPs were investigated following IV and IT administration. Dox-loaded GA-Au NPs had a loading efficiency of 91%, a small particle size (≈50 nm), a promising zeta potential (-20 mV) and a sustained drug release profile at pH 5.3. GA-Au NPs exhibited increased anti-proliferative activity, with approximately a four-fold lower IC value (0.15 μg/ml) than free DOX. The optimized radiolabeling efficiency of Tc-DOX was ≈93%. It showed good physiological stability in mice serum for at least 8 h. The IT delivery of Tc-DOX-loaded GA-Au NPs in tumor-induced mice showed dramatic tumor accumulation. A maximum magnitude of 86.73%ID/g was achieved, at 15 min post-injection, with a target/non-target ratio of ≈56. Tc-DOX-loaded GA-Au NPs could be used for the selective IT delivery of a chemotherapeutic agent and an imaging agent to a target organ.