免疫原性细胞死亡（ICD）的诱导是癌症免疫治疗的一种有前景的策略。 桔梗苷具有潜在的抗癌作用，但由于其不溶于水，临床应用受到限制。 本研究旨在利用聚乙二醇－聚（α-苄氧羧酸－ε-己内酯）（PBCL）纳米颗粒（NPs）制备桔梗苷，并比较其抗癌和诱导ICD的效果与游离桔梗苷。 使用共溶剂蒸发法制备了装载桔梗苷的NPs。 利用紫外光谱、动态光散射和透析袋法分别评估了封装效率（EE）、颗粒大小、聚分散指数（PDI）和药物释放特性。 使用MTT和尝试蓝排除实验评估了药物的抗癌效果。 利用流式细胞术评估了凋亡和钙粒蛋白（CRT）的表达。 利用ELISA和Western blot检测了热休克蛋白90（HSP90）、A1外泌蛋白、GRP78（葡萄糖相关蛋白78）和活化的内质网相关蛋白激酶R样蛋白激酶（p-PERK）。 装载桔梗苷的PEG-PBCL NPs（桔梗苷-PEG-PBCL）显示出97±1％的EE。 桔梗苷-PEG-PBCL的大小为38.18±3.96 nm，PDI为0.62±0.23。 桔梗苷-PEG-PBCL表现出初始迅速释放，随后持续释放24小时。 桔梗苷-PEG-PBCL在B16细胞中显示出明显更强的抗癌效果。 桔梗苷-PEG-PBCL被发现更能诱导细胞凋亡。 游离桔梗苷和桔梗苷NPs均通过增加ICD生物标志物的水平来诱导ICD。 有趣的是，桔梗苷NPs被发现是更强的诱导ICD的剂量。 这些发现表明，桔梗苷和桔梗苷-PEG-PBCL NPs可以在B16细胞中诱导ICD。 PEG-PBCL NPs显著增强了桔梗苷诱导ICD的效力，与其游离形式相比。 © 2023. 作者（们）在Springer Science+Business Media, LLC的独家许可下，属于Springer Nature的一部分。

Induction of immunogenic cell death (ICD) is a promising strategy for cancer immunotherapy. Chrysin, which has potential anticancer effects, faces limitations in clinical applications due to its poor water solubility. This study aimed to formulate chrysin with PEG-poly(α-benzylcarboxylate-ε-caprolactone) (PBCL) nanoparticles (NPs) and assess their anticancer and ICD-inducing potency in melanoma cells, comparing with free chrysin. The co-solvent evaporation method was employed to develop chrysin-loaded NPs. UV spectroscopy, dynamic light scattering, and the dialysis bag method were used to evaluate the encapsulation efficiency (EE), particle size, polydispersity index (PDI), and drug release profile, respectively. The anticancer effects of the drugs were assessed using the MTT and trypan blue exclusion assays. Flow cytometry was employed to evaluate apoptosis and calreticulin (CRT) expression. ELISA and western blotting were used to detect heat shock protein 90 (HSP90), Annexin A1, GRP78 (Glucose-related protein78), and activated protein kinase R-like endoplasmic reticulum kinase (p-PERK). Chrysin-loaded PEG-PBCL NPs (chrysin-PEG-PBCL) showed an EE of 97 ± 1%. Chrysin-PEG-PBCL was 38.18 ± 3.96 nm in size, with a PDI being 0.62 ± 0.23. Chrysin-PEG-PBCL showed an initial burst release, followed by sustained release over 24 h. Chrysin-PEG-PBCL exhibited a significantly stronger anticancer effect in B16 cells. Chrysin-PEG-PBCL was found to be more potent in inducing apoptosis. Both free chrysin and chrysin NPs induced ICD as indicated by an increase in the levels of ICD biomarkers. Interestingly, chrysin NPs were found to be more potent inducers of ICD than the free drug. These findings demonstrate that chrysin and chrysin-PEG-PBCL NPs can induce ICD in B16 cells. PEG-PBCL NPs significantly enhanced the potency of chrysin in inducing ICD compared to its free form.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.