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纳米螯合技术合成的 BCc1 纳米药物在荷乳腺癌小鼠中的免疫机制:免疫调节与肿瘤抑制。

Immunologic Mechanisms of BCc1 Nanomedicine Synthesized by Nanochelating Technology in Breast Tumor-bearing Mice: Immunomodulation and Tumor Suppression.

机构信息

Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.

Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

出版信息

Anticancer Agents Med Chem. 2024;24(19):1442-1456. doi: 10.2174/0118715206302153240723053521.

DOI:10.2174/0118715206302153240723053521
PMID:39069805
Abstract

INTRODUCTION

The side effects of anti-cancer chemotherapy remain a concern for patients. So, designing alternative medications seems inevitable. In this research, the immunological mechanisms of BCc1 nanomedicine on tumor-bearing mice were investigated.

METHODS

BALB/c mice underwent tumor transplantation and were assigned into four groups. Group 1 was orally administered with PBS buffer, Group 2 was orally administered BCc1 10 mg/kg, and Group 3 was orally administered BCc1 40 mg/kg daily, respectively. In addition, a group of mice was administered Cyclophosphamide, 20 mg/kg daily. The weight and tumor volume of mice were evaluated bi-weekly. After 24 days of treatment, cytokines and CTL assay in the spleen cell and the tumor were assessed. Furthermore, the spleen, liver, kidney, lung, gut, and uterine tissue were stained with hematoxylin and eosin. Finally, the tumor samples were stained and analyzed for FOXP3. The survival rate of mice was recorded.

RESULTS

The results confirmed the histological safety of BCc1. This nanomedicine, especially BCc1 10 mg/kg, led to a strong IFN-γ response and suppressed TGF-β cytokine. The frequency of Treg in the tumor tissue of BCc1 nanomedicine groups was decreased. In addition, nanomedicine repressed tumor volume and tumor weight significantly, which was comparable to Cyclophosphamide. These immunologic events increased the survival rate of BCc1-treated groups. The results indicate that BCc1 nanomedicine can suppress tumor growth and thereby increase the survival rate of experimental mice.

CONCLUSION

It seems a modulation in the tumor microenvironment and polarization toward a Th1 response may be involved. So, BCc1 nanomedicine is efficient for human cancer therapy.

摘要

简介

抗癌化疗的副作用仍然是患者关注的问题。因此,设计替代药物似乎是不可避免的。在这项研究中,研究了 BCc1 纳米药物对荷瘤小鼠的免疫学机制。

方法

BALB/c 小鼠进行肿瘤移植,并分为四组。第 1 组口服 PBS 缓冲液,第 2 组口服 BCc1 10mg/kg,第 3 组每日口服 BCc1 40mg/kg,第 4 组每日口服环磷酰胺 20mg/kg。每周评估两次小鼠的体重和肿瘤体积。治疗 24 天后,评估脾细胞和肿瘤中的细胞因子和 CTL 测定。此外,用苏木精和伊红染色脾、肝、肾、肺、肠和子宫组织。最后,对肿瘤样本进行 FOXP3 染色和分析。记录小鼠的存活率。

结果

结果证实了 BCc1 的组织学安全性。这种纳米药物,特别是 BCc1 10mg/kg,导致强烈的 IFN-γ 反应,并抑制 TGF-β 细胞因子。BCc1 纳米药物组肿瘤组织中的 Treg 频率降低。此外,纳米药物显著抑制肿瘤体积和肿瘤重量,与环磷酰胺相当。这些免疫事件提高了 BCc1 治疗组的存活率。结果表明,BCc1 纳米药物可抑制肿瘤生长,从而提高实验小鼠的存活率。

结论

似乎涉及肿瘤微环境的调节和向 Th1 反应的极化。因此,BCc1 纳米药物可有效用于人类癌症治疗。

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