Abstract: Objective　To study the inhibition of tumor growth in 4T1 tumor-bearing mice after administration of doxorubicin hydrochloride cell membrane biomimetic nanoparticles (DOX-CM-NPs), doxorubicin hydrochloride liposomes (DOX-Lips) combined with lentinan (LNT) pharmacological effects.Methods　A 4T1 breast cancer mouse tumor model was established, and the tumor-bearing mice were divided into 0.9% sodium chloride solution group, DOX·HCl group, DOX-Lips group, DOX-CM NPs group, LNT group, DOX·HCl+LNT group, and DOX- Lips+LNT group, DOX-CM-NPs+LNT group, 6 mice per group. The administration doses of DOX·HCl, DOX-Lips and DOX-CM-NPs were calculated as equivalent DOX·HCl at 2 mg/kg. The administration method was tail vein injection. The administration volume was 0.2 mL/animal and was administered once every two days. The dosage concentration of lentinan tablet suspension is 0.2 g/kg, the dosage method was intragastric administration, the dosage volume was 0.2 mL/animal, and it was administered once a day. Preliminary evaluation of pharmacodynamics and toxicity in vivo is carried out. The immunomodulatory effect was evaluated by ELISA method.Results　The inhibitory effect of DOX-CM-NPs on 4T1 tumor-bearing mice was significantly better than that of the physiological 0.9% sodium chloride solution group (P<0.001), the DOX·HCl group (P<0.01) and the DOX-Lips group (P<0.01), and combined with LNT. The inhibitory effect is further strengthened after treatment and has a synergistic effect; preliminary evaluation of toxicity and immunomodulatory effect indicate that LNT It can be regulated by significantly up regulating the expression of interleukin-2 (IL-2) (P<0.05) and interferon (IFN-γ) (P<0.01) and reducing the expression of tumor necrosis factor (TNF-α) (P<0.01). Conclusion　In vivo drug efficacy study, DOX-CM-NPs have a stronger tumor-inhibiting effect than DOX·HCl and DOX-Lips, and it has a synergistic effect on the treatment of 4T1 tumor-bearing mice after combined with LNT.

Key words: doxorubicin hydrochloride cell membrane biomimetic nanoparticles, doxorubicin hydrochloride liposomes, lentinan, breast cancer, combination medication

摘要： 目的　研究盐酸阿霉素细胞膜仿生纳米粒(DOX-CM-NPs)、盐酸阿霉素脂质体(DOX-Lips)联合香菇多糖 (LNT)给药后对 4T1 荷瘤小鼠肿瘤生长抑制的药理作用。方法　建立 4T1 乳腺癌小鼠肿瘤模型,将荷瘤小鼠分为 0.9%氯化钠注射液组、DOX·HCl组、DOX-Lips组、DOX-CM-NPs组、LNT组、DOX·HCl+LNT组、DOX-Lips+LNT组、 DOX-CM-NPs+LNT组,每组6只。DOX·HCl、DOX-Lips和DOX-CM-NPs给药剂量统一设定为2 mg/kg,给药剂量以 制剂所载盐酸阿霉素的量进行折算,给药方式为尾静脉注射,给药体积为0.2 mL/只,每隔两天给药1次。香菇多 糖片混悬液的给药浓度为0.2 g/kg,给药方式为灌胃给药,给药体积为0.2 mL/只,每天给药1次,进行体内药效学 和毒性初步评价,采用ELISA法评价免疫调节作用。结果　DOX-CM-NPs组对4T1荷瘤鼠肿瘤的抑制效果显著优 于0.9%氯化钠注射组(P<0.001)、DOX·HCl组(P<0.01)和 DOX-Lips组(P<0.01),并且联合 LNT 给药后抑制效 果进一步加强,且具有协同增效的作用;毒性初步评价和免疫调节作用评价表明,LNT可以通过显著上调白细胞介 素2(IL-2)(P<0.05)、干扰素(IFN-γ)(P<0.01)表达,降低肿瘤坏死因子(TNF-α)(P<0.01)表达,调节免疫功能。 结论　在体内药效研究中,DOX-CM-NPs抑瘤效果强于DOX·HCl和DOX-Lips,联合LNT给药后对4T1荷瘤小鼠治 疗具有协同增效作用。

关键词: 盐酸阿霉素细胞膜仿生纳米粒, 盐酸阿霉素脂质体, 香菇多糖, 乳腺癌, 联合用药