Nano-encapsulated tryptanthrin derivative for combined anticancer therapy via inhibiting indoleamine 2,3-dioxygenase and inducing immunogenic cell death

纳米封装色胺酮衍生物通过抑制吲哚胺2,3-双加氧酶和诱导免疫原性细胞死亡进行联合抗癌治疗

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作者:Canyu Yang, Bing He, Qiang Zheng, Dakuan Wang, Mengmeng Qin, Hua Zhang, Wenbing Dai, Qiang Zhang, Xiangbao Meng, Xueqing Wang

Aim

We developed a polycaprolactone-based nanoparticle (NP) to encapsulate tryptanthrin derivative CY-1-4 and evaluated its antitumor efficacy. Materials &

Conclusion

CY-1-4 is a potential antitumor candidate that could act as a single agent with combined functions of IDO inhibition and ICD induction.

Methods

CY-1-4 NPs were prepared and evaluated for their cytotoxicity and associated mechanisms, indoleamine 2,3-dioxygenase (IDO)-inhibitory ability, immunogenic cell death (ICD)-inducing ability and antitumor efficacy.

Results

CY-1-4 NPs were 123 nm in size. In vitro experiments indicated that they could both induce ICD and inhibit IDO. In vivo studies indicated that a medium dose reduced 58% of the tumor burden in a B16-F10-bearing mouse model, decreased IDO expression in tumor tissues and regulated lymphocytes subsets in spleen and tumors.

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