Yongmei Zhao, Nicholas L. Fletcher, Anna Gemmell, Zachary H. Houston, Idriss Blakey, Tianqing Liu, Kristofer J. Thurecht
Publication year: 2019

37th Australasian Polymer Symposium – Novotel Twin Waters, Twin Waters, QLD, Australia. 10th – 13th of November, 2019.

Chemotherapetics such as doxorubicin (DOX) are of interest to work as synergistic pairs with enzyme inhibitors (camptothecin, CPT) to increase the efficacy of treatment. We have prepared a hyperbranched polymer dual-theranostic system with site-specific synergistic delivery of two drugs on a single construct. The nanotheranostic also contained Cy5 as an imaging tracer and was targeted using a bisbepcific antibody with affinity for breast cancer.  The carrier exhibited release of both molecules in two-time scales by exploiting both redox and hydrolytic mechanisms for CPT and DOX, respectively. The release of the drug and cellular uptake were validated in vitro, and intracellular trafficking was also investigated with confocal microscopy. Both the targeting towards epidermal growth factor receptor (EGFR) and the synergistic release of drugs lead to an enhanced therapeutic response with no observable adverse effects on the mouse health.  The results show promising potential for this system as a synergistic treatment for breast cancer.

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