Ganoderma lucidum spore oil (GLSO) has been long practiced and widely recognized as a healthy food composite performing potential anticancer and antioxidant activity. However, its further application might be limited by the native poorly soluble and instable properties. Herein, size-tunable GLSO nanosystems have been designed and tailored to three sizes of particles at 20 nm, 40 nm and 80 nm by high-pressure homogenization, for achieving robust therapeutic effect against cancer cells. As expected, toxicity of biocompatible different-sized GLSO@NEs on MGC803 cancer cells significantly enhanced, thanks to the improved cellular uptake and retention efficacy of GLSO@NEs. In addition, middle-sized 40 nm-GLSO@NEs performed superior permeability across Caco-2 intestinal absorption barrier to improve internalized quantity of GLSO. More importantly, GLSO@NEs could effectively prevent cell migration and invasion, simultaneously activating caspase activity to trigger cell death. Interestingly, middle size of 40 nm-GLSO@NEs performed superior accumulation efficacy in cells. Ultimately, 40 nm-GLSO@NEs showed potent suppression effect on tumors in vivo, effectively reversing liver and kidney damage induced by cancer, which was accompanied with no obvious toxicity and side effects during treatment. Therefore, this study not only provides a simple method for preparation of GLSO-like traditionally functional composite by high-pressure homogenization, but also sheds light on the application in future clinical cancer therapy.

灵芝孢子油（GLSO）已被长期实践，并被广泛认为是一种健康的食品复合材料，具有潜在的抗癌和抗氧化活性。但是，其进一步的应用可能会受到天然的难溶和不稳定特性的限制。在本文中，已经通过高压均质化将尺寸可调的GLSO纳米系统设计和定制为20nm，40nm和80nm的三种尺寸的颗粒，以实现针对癌细胞的鲁棒的治疗效果。不出所料，由于改善了GLSO @ NEs的细胞摄取和保留功效，生物相容性大小不同的GLSO @ NEs对MGC803癌细胞的毒性显着增强。此外，中等大小的40 nm-GLSO @ NEs在Caco-2肠吸收屏障上表现出优异的渗透性，从而改善了GLSO的内在量。更重要的是，GLSO @ NEs可以有效防止细胞迁移和侵袭，同时激活caspase活性以触发细胞死亡。有趣的是，中等大小的40 nm-GLSO @ NEs在细胞中表现出优异的积累功效。最终，40 nm-GLSO @ NEs对肿瘤表现出有效的抑制作用在体内，有效逆转了由癌症引起的肝肾损害，在治疗过程中没有明显的毒性和副作用。因此，本研究不仅提供了一种通过高压均质法制备类似GLSO的传统功能性复合物的简单方法，而且为将来在临床癌症治疗中的应用提供了启示。