JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2023
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IF 9.9
Zhijin Fan,Xiaoxiao Jiang,Tong Sun,Fanchu Zeng,Guojia Huang,Changhong Liang,Liming Nie
Tumor-associated macrophages (TAMs) are vital in the tumor microenvironment, contributing to immunosuppression and therapy tolerance. Despite their importance, the precise re-education of TAMs in vivo continues to present a formidable challenge. Moreover, the lack of real-time and efficient methods to comprehend the spatiotemporal kinetics of TAMs repolarization remains a significant hurdle, severely hampering the accurate assessment of treatment efficacy and prognosis. Herein, we designed a metal–organic frameworks (MOFs) based Caspase-1 nanoreporter (MCNR) that can deliver a TLR7/8 agonist to the TAMs and track time-sensitive Caspase-1 activity as a direct method to monitor the initiation of immune reprogramming. This nanosystem exhibits excellent TAMs targeting ability, enhanced tumor accumulation, and stimuli-responsive behavior. By inducing the reprogramming of TAMs, they were able to enhance T -cell infiltration in tumor tissue, resulting in inhibited tumor growth and improved survival in mice model. Moreover, MCNR also serves as an activatable photoacoustic and fluorescent dual-mode imaging agent through Caspase-1-mediated specific enzyme digestion. This feature enables non-invasive and real-time antitumor immune activation monitoring. Overall, our findings indicate that MCNR has the potential to be a valuable tool for tumor immune microenvironment remodeling and noninvasive quantitative detection and real-time monitoring of TAMs repolarization to immunotherapy in the early stage.
研究领域:
癌症生物学
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免疫学
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纳米技术
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生物医学工程
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Liqun Jiang,Ziyao Wang,Yan Wang,Shuo Liu,Ya Xu,Cong Zhang,Lei Li,Sujia Si,Bingmei Yao,Wenjin Dai,Huiyang Li
The re-education of tumor-associated macrophages (TAMs) is an effective strategy to inhibit the growth and metastasis of lung cancer. We have reported that chitosan could re-educate the TAMs and then inhibit cancer metastasis; however, the re-exposure of chitosan from the chemical corona on their surface is critical for this effect. In this study, a strategy was proposed to re-expose the chitosan from chemical corona, and a sustained H 2 S generation was applied to enhance the immunotherapy of chitosan. To achieve this objective, an inhalable microsphere (namely F/Fm) was designed, which could be degraded by the matrix metalloproteinase in lung cancer, releasing two kinds of nanoparticles ; in an external magnetic field, these nanoparticles can aggregate with each other, and β-cyclodextrin on the surface of one nanoparticle can be hydrolyzed by amylase on the surface of another nanoparticle, leading to the re-exposure of chitosan in the inner layer of β-cyclodextrin and the release of diallyl trisulfide for H 2 S generation. In vitro , the expression of CD86 and secretion of TNF-α by TAMs was increased by F/Fm, proving the re-education of TAMs, and the apoptosis of A549 cells was promoted with the migration and invasion being inhibited. In the Lewis lung carcinoma-bearing mouse, the F/Fm re-educated the TAMs and provided a sustained generation of H 2 S in the region of lung cancer, effectively inhibiting the growth and metastasis of lung cancer cells. This work provides a new strategy for the treatment of lung cancer in combination of re-education of TAMs by chitosan and the adjuvant chemotherapy by H 2 S.
研究领域:
癌症生物学
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药学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
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IF 11.467
Yanjuan Huang,Zilin Guan,Lingling Ren,Yong Luo,Meixu Chen,Yue Sun,Yuanfeng He,Zishan Zeng,Xiuling Dai,Jingwen Jiang,Zeqian Huang,Chunshun Zhao
Chemodynamic therapy (CDT), an emerging tumor-specific therapeutic modality, is frequently restrained by insufficient intratumoral Fenton catalysts and increasingly inefficient catalysis caused by the continuous consumption of limited H 2 O 2 within tumors. Herein, we engineered a pH-responsive bortezomib (BTZ) polymer prodrug catalytic nanoreactor (He [email protected] ) capable of self-supplying Fenton catalyst and H 2 O 2 . It is aimed for tumor-specific chemo/chemodynamic therapy via oxidative stress and endoplasmic reticulum (ER) stress dual-amplification and macrophage repolarization. A catechol‑boronate bond-based hyaluronic acid-BTZ prodrug HA-DA-BTZ was modified on Hemin and Zn 2+ coordination nanoscale framework (He Zn), an innovative CDT inducer, to construct [email protected] [email protected] with good stability and superior peroxidase-like activity preferentially accumulated at tumor sites and be actively internalized by tumor cells. Under the cleavage of catechol‑boronate bond in acidic endo/lysosomes, pre-masked BTZ was rapidly released to induce ubiquitinated protein aggregation, robust ER stress and elevated H 2 O 2 levels. The amplified H 2 O 2 was further catalyzed by He Zn via Fenton-catalytic reactions to produce hypertoxic •OH, enabling cascaded oxidative stress amplification and long-lasting effective CDT, which in turn aggravated BTZ-induced ER stress. Eventually, a dual-amplification of oxidative stress and ER stress was achieved to initiate cell apoptosis/necrosis with reduced BTZ toxicity. Intriguingly, [email protected] could repolarize macrophages from M2 to antitumor M1 phenotype for potential tumor therapy. This “all in one” prodrug nanocatalytic reactor not only enriches the CDT inducer library, but provides inspirational strategy for simultaneous oxidative stress and ER stress based excellent cancer therapy.
研究领域:
癌症治疗
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纳米技术
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药物科学
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免疫学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）