Co-delivery of siRNA and doxorubicin to cancer cells from additively manufactured implants

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Abstract

Tumors in load bearing bone tissue are a major clinical problem, in part because surgical resection invokes a dilemma whether to resect aggressively, risking mechanical failure, or to resect conservatively, risking cancer recurrence due to residual malignant cells. A chemo-functionalized implant, capable of physically supporting the void while killing residual cancer cells, would be an attractive solution. Here we describe a novel additively manufactured implant that can be functionalized with chitosan/siRNA nanoparticles. These induce long term gene silencing in adjacent cancer cells without showing toxicity to normal cells. When scaffolds are functionalized with siRNA/chitosan nanoparticles and doxorubicin in combination, their effects synergized leading to cancer cell death. This technology may be used to target resistance genes by RNA interference and thereby re-sensitizing the cancer cells to co-delivered chemotherapy.

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Chen, M., Andersen, M., Dillschneider, P., Chang, C. C., Gao, S., Le, D. Q. S., … Kjems, J. (2015). Co-delivery of siRNA and doxorubicin to cancer cells from additively manufactured implants. RSC Advances, 5(123), 101718–101725. https://doi.org/10.1039/c5ra23748c

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