← 返回

靶向骨肉瘤中髓系细胞的纳米药物在增强免疫治疗中的潜在靶点与应用

英文原题:Potential targets and applications of nanodrug targeting myeloid cells in osteosarcoma for the enhancement of immunotherapy.

查看英文原题

Potential targets and applications of nanodrug targeting myeloid cells in osteosarcoma for the enhancement of immunotherapy.

PubMed 2023/09/21(内容时间) Front Pharmacol Q1 · IF 5.4(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

靶向免疫疗法已成为癌症治疗中的一种变革性方法,能够提高对肿瘤细胞的特异性,并最大限度地减少对健康组织的损伤。肿瘤免疫系统的靶向治疗已进入临床应用阶段,在早期和晚期恶性肿瘤中均展现出显著的抗肿瘤活性,进而提高了长期生存率。针对肿瘤免疫系统最常见且最重要的靶向治疗是通过使用检查点抑制剂抗体和CAR-T 细胞治疗来实现的。

然而,在骨肉瘤等实体瘤中使用免疫治疗药物或联合治疗时,由于疗效有限或诱导严重细胞毒性,面临诸多挑战。利用纳米颗粒药物递送系统靶向肿瘤相关巨噬细胞和骨髓来源抑制细胞是一种有前景且具有吸引力的免疫治疗策略。这是因为这些骨髓细胞常在肿瘤微环境中发挥免疫抑制作用,促进肿瘤进展、转移及耐药性的产生。

此外,鉴于髓系细胞倾向于吞噬纳米颗粒和微颗粒,它们是合理的治疗靶点。因此,我们讨论了基于纳米医学通过靶向骨肉瘤中的髓系细胞增强免疫治疗的机制,以及相关治疗策略如何从以下角度很好地适应免疫治疗:利用纳米颗粒促进免疫原性细胞死亡、调节肿瘤相关巨噬细胞中各种细胞亚群的比例、与髓系细胞受体配体相互作用、激活免疫刺激性信号通路、改变髓系细胞表观遗传学以及调节免疫刺激强度。我们还探讨了基于纳米医学的免疫治疗的临床实施。

展开英文摘要原文

Targeted immunotherapies have emerged as a transformative approach in cancer treatment, offering enhanced specificity to tumor cells, and minimizing damage to healthy tissues. The targeted treatment of the tumor immune system has become clinically applicable, demonstrating significant anti-tumor activity in both early and late-stage malignancies, subsequently enhancing long-term survival rates.

The most frequent and significant targeted therapies for the tumor immune system are executed through the utilization of checkpoint inhibitor antibodies and chimeric antigen receptor T cell treatment.

However, when using immunotherapeutic drugs or combined treatments for solid tumors like osteosarcoma, challenges arise due to limited efficacy or the induction of severe cytotoxicity. Utilizing nanoparticle drug delivery systems to target tumor-associated macrophages and bone marrow-derived suppressor cells is a promising and attractive immunotherapeutic approach. This is because these bone marrow cells often exert immunosuppressive effects in the tumor microenvironment, promoting tumor progression, metastasis, and the development of drug resistance.

Moreover, given the propensity of myeloid cells to engulf nanoparticles and microparticles, they are logical therapeutic targets.

Therefore, we have discussed the mechanisms of nanomedicine-based enhancement of immune therapy through targeting myeloid cells in osteosarcoma, and how the related therapeutic strategies well adapt to immunotherapy from perspectives such as promoting immunogenic cell death with nanoparticles, regulating the proportion of various cellular subgroups in tumor-associated macrophages, interaction with myeloid cell receptor ligands, activating immunostimulatory signaling pathways, altering myeloid cell epigenetics, and modulating the intensity of immunostimulation.

We also explored the clinical implementations of immunotherapy grounded on nanomedicine.

论文信息

作者
Zhu J、Fan J、Xia Y、Wang H、Li Y、Feng Z、Fu C
单位
Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China.China
文献类型
综述
期刊
Frontiers in pharmacology2023
原文标识
PubMed 37808190 · DOI 10.3389/fphar.2023.1271321