Biodegradable silk fibroin membranes for potential localized treatment of melanoma: optimized preparation andin vitrostudy.

Abstract

As a lethal skin cancer, melanoma is highly aggressive and metastatic with high recurrence rates and the common therapy is surgical resection followed by chemotherapy. To minimize the side effects of chemotherapeutic drugs and prevent tumor recurrencein situ, localized therapy is a more suitable treatment method. Here, a fully biodegradable silk fibroin (SF) membrane loaded with the therapeutic drug doxorubicin (Dox) is fabricated for potential localized chemotherapy of melanoma. SF has a high loading capacity of Dox with a maximum mass ratio of Dox/SF equal to 2.5% without generating precipitates. Water annealing (WA) is utilized to enhance the membrane's stability in the aqueous environment by inducing the formation ofβ-sheets and the treated membrane was stable in water for at least 15 d. Meanwhile, both the ultimate tensile strength and Young's modulus of the SF membrane were significantly enhanced after the WA. When incubated with Proteinase K, the mass loss of water-treated membranes followed a linear trend and the degradation coefficient was -30.39, -25.31, and -18.62 for 1 ml, 2 ml, and 3 ml membranes respectively. All the water-treated membranes could be fully degraded within 5 h. By adjusting the membrane thickness and Dox amount, precisely controlled sustained release of Dox is achieved with an initial release rate of 10.39-80.65 μg h^-1. The fabricated SF-Dox membrane demonstrates excellent therapeutic effects on melanoma cells with the lowest viability of 51.59% after 24 h and 9.48% after 48 h while being highly biocompatible with normal cells. These findings highlight the potential of SF-Dox membranes as an effective localized therapeutic strategy for melanoma, warranting further investigation in preclinical and clinical settings. This work provides a novel paradigm not only for the development of localized therapy of melanoma but also for the postoperative care systems after melanoma surgical excision.