Metal–Organic Framework-Based Nano-Activators Facilitating Microwave Combined Therapy via a Divide-and-Conquer Tactic for Triple-Negative Breast Cancer

癌症研究 三阴性乳腺癌 肿瘤微环境 PI3K/AKT/mTOR通路 MAPK/ERK通路 免疫系统 免疫疗法 免疫检查点 乳腺癌 医学 癌症 免疫学 信号转导 生物 内科学 细胞生物学
作者
Qiong Wu,Longfei Tan,Xiangling Ren,Changhui Fu,Zengzhen Chen,Jun Ren,Tengchuang Ma,Xianwei Meng
出处
期刊:ACS Nano [American Chemical Society]
卷期号:17 (24): 25575-25590 被引量:4
标识
DOI:10.1021/acsnano.3c09734
摘要

Aiming at the clinical problems of high recurrence and metastasis rate of triple-negative breast cancer, a divide-and-conquer tactic is developed. The designed nanoactivators enhance microwave thermo-dynamic-chemotherapy to efficiently kill primary tumors, simultaneously ameliorate the immunosuppressive microenvironment, activate the tumor infiltration of T lymphocytes, and enhance the accumulation and penetration of PD-1/PD-L1 immune agents, ultimately boosting the efficacy of immune checkpoint blocking therapy to achieve efficient inhibition of distal tumors and metastases. Metal-organic framework (MOF)-based MPPT nano-activator is synthesized by packaging chemotherapeutic drug Pyrotinib and immunosuppressant PD-1/PD-L1 inhibitor 2 into MnCa-MOF and then coupling target molecule triphenylphosphine, which significantly improved the accumulation and penetration of Pyrotinib and immunosuppressant in tumors. In addition to the combined treatment of microwave thermo-dynamic-chemotherapy under microwave irradiation, Mn2+ in the nano-activator comprehensively promotes the cGAS-STING pathway to activate innate immunity, microwave therapy, and hypoxia relief are combined to ameliorate the tumor immunosuppressive microenvironment. The released Pyrotinib down-regulates epidermal growth factor receptor and its downstream pathways PI3K/AKT/mTOR and MAPK/ERK signaling pathways to maximize the therapeutic effect of immune checkpoint blocking, which helps to enhance the antitumor efficacy and promote long-term memory immunity. This nano-activator offers a generally promising paradigm for existing clinical triple-negative breast cancer treatment through a divide-and-conquer strategy.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
蓝天完成签到,获得积分10
刚刚
zhangcz发布了新的文献求助10
刚刚
王一一完成签到,获得积分10
刚刚
刚刚
1秒前
1秒前
酷波er应助倾慕采纳,获得10
1秒前
宜醉宜游宜睡完成签到,获得积分0
2秒前
完美世界应助研友_LNMPD8采纳,获得10
2秒前
852应助艾云欣采纳,获得10
2秒前
JamesPei应助malus采纳,获得10
3秒前
干净的烧鹅完成签到,获得积分10
3秒前
5秒前
Jox完成签到,获得积分10
5秒前
张先生发布了新的文献求助10
5秒前
无花果应助文艺点点采纳,获得10
6秒前
9秒前
9秒前
筱筱完成签到 ,获得积分20
9秒前
9秒前
宁毅完成签到,获得积分10
9秒前
物质决定意识完成签到,获得积分10
9秒前
10秒前
fiona7777发布了新的文献求助10
10秒前
田様应助科研通管家采纳,获得10
10秒前
Owen应助科研通管家采纳,获得10
10秒前
小马甲应助科研通管家采纳,获得10
10秒前
10秒前
科研通AI2S应助科研通管家采纳,获得10
10秒前
菜籽完成签到,获得积分10
10秒前
11秒前
张张发布了新的文献求助10
11秒前
12秒前
海盐气泡水完成签到,获得积分10
12秒前
张晓完成签到 ,获得积分10
13秒前
艾云欣发布了新的文献求助10
14秒前
小确幸完成签到,获得积分10
14秒前
Harry发布了新的文献求助10
15秒前
倾慕发布了新的文献求助10
15秒前
Owen应助敬老院N号采纳,获得10
15秒前
高分求助中
Impact of Mitophagy-Related Genes on the Diagnosis and Development of Esophageal Squamous Cell Carcinoma via Single-Cell RNA-seq Analysis and Machine Learning Algorithms 2000
Evolution 1100
How to Create Beauty: De Lairesse on the Theory and Practice of Making Art 1000
Research Methods for Sports Studies 1000
Gerard de Lairesse : an artist between stage and studio 670
T/CAB 0344-2024 重组人源化胶原蛋白内毒素去除方法 500
[Procedures for improving absorption properties of polystyrene microtest plates by coating with nitrocellulose] 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 2981071
求助须知:如何正确求助?哪些是违规求助? 2642454
关于积分的说明 7130061
捐赠科研通 2275477
什么是DOI,文献DOI怎么找? 1207138
版权声明 592045
科研通“疑难数据库(出版商)”最低求助积分说明 589713