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载阿霉素纤维素纳米粒对兔VX2肝肿瘤模型的抗肿瘤作用

Antitumor Effects of Doxorubicin-Loaded Cellulose Nanoparticles in the Rabbit VX2 Liver Tumor Model.

作者信息

Lee Joonhyuk, Kim Kun Yung, Lee Chong-Ho, Yoon Chang Jin, Lee Hak Jong, Kim Dongyeon, Kim Minuk, Chung Jin Wook, Lee Jae Hwan

机构信息

Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea.

Department of Radiology, Seoul National University College of Medicine, Daehak-ro, Jongno-gu, Seoul, Republic of Korea.

出版信息

Cardiovasc Intervent Radiol. 2025 Sep 9. doi: 10.1007/s00270-025-04170-z.

Abstract

PURPOSE

To evaluate the preclinical efficacy and safety of transarterial chemoembolization (TACE) using doxorubicin-loaded biocompatible cellulose nanoparticles in a rabbit VX2 liver tumor model.

MATERIALS AND METHODS

Following institutional animal care committee approval, 23 rabbits with VX2 liver tumors were randomized into three groups: Group A (n = 9) received doxorubicin-loaded cellulose nanoparticles with ethiodized oil; Group B (n = 9) received doxorubicin with ethiodized oil; and Group C (n = 5) served as untreated controls. Tumor size was monitored via ultrasound for 4 weeks, and serum liver enzymes (aspartate transaminase and alanine transaminase) were measured on days 1, 3, and 7 to assess hepatotoxicity. An additional 10 healthy rabbits were randomized into two groups: Group D (n = 5) received doxorubicin-loaded cellulose nanoparticles with ethiodized oil, and Group E (n = 5) received doxorubicin with ethiodized oil, to measure serum doxorubicin concentrations up to 30 min post-treatment.

RESULTS

Group A demonstrated significantly slower overall tumor growth compared to Group C (p = 0.005) and slower growth between days 24 and 27 compared to Group B (p = 0.037). Pharmacokinetic analysis showed significantly lower serum doxorubicin levels in Group D than Group E at 2 and 5 min post-delivery (p < 0.05). Hepatotoxicity peaked at 24 h, with significantly lower alanine transaminase levels in Group A compared to Group B (p = 0.025), normalizing by day 7.

CONCLUSION

TACE using doxorubicin-loaded cellulose nanoparticles demonstrated promising preclinical efficacy and safety compared to conventional TACE.

LEVEL OF EVIDENCE

No level of evidence, Animal Study.

摘要

目的

在兔VX2肝肿瘤模型中评估使用载有多柔比星的生物相容性纤维素纳米颗粒的经动脉化疗栓塞术(TACE)的临床前疗效和安全性。

材料与方法

经机构动物护理委员会批准后,将23只患有VX2肝肿瘤的兔子随机分为三组:A组(n = 9)接受载有多柔比星的纤维素纳米颗粒与乙碘油;B组(n = 9)接受多柔比星与乙碘油;C组(n = 5)作为未治疗的对照组。通过超声监测肿瘤大小4周,并在第1、3和7天测量血清肝酶(天冬氨酸转氨酶和丙氨酸转氨酶)以评估肝毒性。另外10只健康兔子随机分为两组:D组(n = 5)接受载有多柔比星的纤维素纳米颗粒与乙碘油,E组(n = 5)接受多柔比星与乙碘油,以测量治疗后30分钟内的血清多柔比星浓度。

结果

与C组相比,A组总体肿瘤生长明显较慢(p = 0.005),与B组相比,在第24至27天生长较慢(p = 0.037)。药代动力学分析显示,给药后2分钟和5分钟时,D组血清多柔比星水平明显低于E组(p < 0.05)。肝毒性在24小时达到峰值,A组丙氨酸转氨酶水平明显低于B组(p = 0.025),至第7天恢复正常。

结论

与传统TACE相比,使用载有多柔比星的纤维素纳米颗粒的TACE显示出有前景的临床前疗效和安全性。

证据水平

无证据水平,动物研究。

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