Abstract
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 99mTc-Doxorubicin (99mTc-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 99mTc (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 99mTc-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 (≈50nm), a promising zeta potential (-20mV) and a sustained drug release profile at pH 5.3. GA-Au NPs exhibited increased anti-proliferative activity, with approximately a four-fold lower IC50 value (0.15μg/ml) than free DOX. The optimized radiolabeling efficiency of 99mTc-DOX was ≈93%. It showed good physiological stability in mice serum for at least 8h. The IT delivery of 99mTc-DOX-loaded GA-Au NPs in tumor-induced mice showed dramatic tumor accumulation. A maximum magnitude of 86.73%ID/g was achieved, at 15min post-injection, with a target/non-target ratio of ≈56. 99mTc-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.
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