Reprogramming Hypoxic Tumor-Associated Macrophages by Nanoglycoclusters for Boosted Cancer Immunotherapy

被引：31

作者：

Zhao, Yong-Dan ^{[1
,2
,3
,4
]}

An, Hong-Wei ^{[2
,3
]}

Mamuti, Muhetaerjiang ^{[2
,3
]}

Zeng, Xiang-Zhong ^{[2
,3
]}

Zheng, Rui ^{[2
,3
]}

Yang, Jia ^{[2
,3
]}

Zhou, Wei ^{[3
,5
]}

Liang, Yuxin ^{[1
,3
]}

Qin, Gege ^{[1
,3
]}

Hou, Da-Yong ^{[2
]}

Liu, Xiaolong ^{[1
,3
]}

Wang, Hao ^{[2
,3
]}

Zhao, Yuliang ^{[2
,3
]}

Fang, Xiaohong ^{[1
,3
,5
]}

机构：

[1] Chinese Acad Sci ICCAS, Inst Chem, CAS Res Educ Ctr Excellence Mol Sci, Key Lab Mol Nanostruct & Nanotechnol, Beijing 100190, Peoples R China

[2] Chinese Acad Sci, Natl Ctr Nanosci & Technol NCNST, Key Lab Biomed Effects Nanomat & Nanosafety, Ctr Excellence Nanosci, Beijing 100190, Peoples R China

[3] Univ Chinese Acad Sci, Sch Chem Sci, Beijing 100049, Peoples R China

[4] Shanxi Med Univ, Sch Pharm, Jinzhong 030009, Shanxi, Peoples R China

[5] Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou 310022, Zhejiang, Peoples R China

来源：

ADVANCED MATERIALS | 2023年 / 35卷 / 24期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

cancer immunotherapy; glycopeptides; hypoxia; nanoglycoclusters; tumor-associated macrophages; BREAST-CARCINOMA; PENETRATION; EXPRESSION; RESPONSES; INVASION;

D O I：

10.1002/adma.202211332

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The tumor-associated macrophages (TAMs) in intratumoral hypoxic regions are key drivers of immune escape. Reprogramming the hypoxic TAMs to antitumor phenotype holds great therapeutic benefits but remains challenging for current drugs. Here, an in situ activated nanoglycocluster is reported to realize effective tumor penetration and potent repolarization of hypoxic TAMs. Triggered by the hypoxia-upregulated matrix metalloproteinase-2 (MMP-2), the nanoglycocluster is self-assembled from the administered mannose-containing precursor glycopeptides and presents densely-arrayed mannoses to multivalently engage with mannose receptors on M2-like TAMs for efficient phenotype switch. By virtue of the high diffusivity of precursor glycopeptides due to their low molecular mass and weak affinity with TAMs in perivascular regions, the nanoglycoclusters are capable of substantially accumulating in hypoxic areas to strongly interact with local TAMs. This enables the efficient repolarization of overall TAMs with a higher rate than the small-molecule drug R848 and CD40 antibody, and beneficial therapeutic effects in mouse tumor models especially when combining with PD-1 antibody. This on-demand activated immunoagent is endowed with tumor-penetrating properties and inspires the design of diverse intelligent nanomedicines for hypoxia-related cancer immunotherapy.

引用

页数：14

共 52 条

[51] Nanomedicine enables spatiotemporally regulating macrophage-based cancer immunotherapy [J].