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Dehui Wan1 Ling-Chu Yang1

1, National Tsing Hua Univ, Hsinchu, , Taiwan

Many therapies, including surgery, chemotherapy and radiotherapy, are used to treat cancer, but most of them do not accomplish the desired purposes. For example, it is still a challenge to efficiently kill cancer cells without hurting normal tissues. Alternatively, photothermal therapy is an approach for local tumor ablation, by using nanoabsorbers to convert near-infrared (NIR) light into heat. In general, the administrated nanoparticles predominantly accumulate in tumor tissue due to the EPR effect. The retention time of nanoparticles is usually short, since they will be removed quickly via lymphatic system. Therefore, intense laser irradiation for one-shot treatment or in combination with chemotherapy is necessary to enhance the efficacy of cancer therapy. However, the tumor accumulation of nanoparticles and drug is still limited due to the blood circulation and organ clearance. To address the problem, injectable hydrogel systems have been used as drug delivery system, which can significantly prolong the retention time of nanoparticles in vivo. Besides, hydrogel can also be used as drug controlled-release platform to enhance the therapeutic effect without damage of normal tissues. Thus, the development of multifunctional hydrogel systems is extremely valuable, especially for combination cancer therapy.
Herein, we developed a novel injectable hydrogel system, by embedding gold nanoshells (GN, NIR-light absorber) and doxorubicin (DOX, anti-cancer drug) into a biodegradable natural polymer, silk fibroin. First, the mixed SF solution was orthotopically injected into the mice bearing with 4T1 breast cancer and followed by laser irradiation. The light-induced heat from the GN would increase the local temperature and induced in situ formation of SF hydrogel through sol-gel transition. In this case, most of GN and DOX could be trapped well within the tumor and thus the retention time of both agents would be significantly prolonged. We observed that the absorbance peak of GN in SF was ca. 800 nm and the local temperature would elevate quickly under NIR-laser irritation. The content of β-sheets in SF increased more rapidly at 50 oC, as compared to that at 37 oC, indicating the laser-induced heating is necessary to induce formation of SF hydrogel. Besides, we also found that Dox could be released successively from SF/DOX hydrogel up to 71 % within 12 days because of the acidic environment, degradation of SF hydrogel, and heat-enhanced diffusion. Then, the photothermal and chemo cytotoxicity of multifunctional hydrogel system in 4T1 breast cancer cells was evaluated with WST-1 and LIVE/DEAD assay. The WST-1 result clearly pointed up that the silk/GN/DOX group exhibited the highest cytotoxicity effect due to the synergistic photothermal-chemotherapy. Further material characterization and in vitro/in vivo evaluations are in progress and will be reported in the conference.

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