Cancer-associated fibroblast-targeted nanodrugs reshape colorectal tumor microenvironments to suppress tumor proliferation, metastasis and improve drug penetration

Shen, Wenqi; Yao, Ping-An; Li, Wenjing; Gu, Changji; Gao, Tian; Cao, Yi; Wang, Zheng; Pei, Renjun; Xing, Chungen

doi:10.1039/d2tb02253b

Cited by 13 publications

(8 citation statements)

References 44 publications

(58 reference statements)

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“…Shen, W., and colleagues designed a nanoemulsion combining chemotherapy and gene therapy to simultaneously deliver doxorubicin and small interfering RNAs targeting hepatocyte growth factor (HGF) to reduce ECM deposition, induce CAF apoptosis, and reduce tumor metastasis. The chemotherapy resistance was ameliorated somewhat, and the tumor progression was inhibited [ 402 ]. Another tyrosine kinase inhibitor, NT157, can pharmacologically inhibit IGF-1R and STAT3 signaling.…”

Section: Background Knowledge Of Cafsmentioning

confidence: 99%

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Zhang,

Yue,

Chen

et al. 2023

Mol Cancer

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Despite centuries since the discovery and study of cancer, cancer is still a lethal and intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as a pivotal component of the tumor microenvironment. The versatility and sophisticated mechanisms of CAFs in facilitating cancer progression have been elucidated extensively, including promoting cancer angiogenesis and metastasis, inducing drug resistance, reshaping the extracellular matrix, and developing an immunosuppressive microenvironment. Owing to their robust tumor-promoting function, CAFs are considered a promising target for oncotherapy. However, CAFs are a highly heterogeneous group of cells. Some subpopulations exert an inhibitory role in tumor growth, which implies that CAF-targeting approaches must be more precise and individualized. This review comprehensively summarize the origin, phenotypical, and functional heterogeneity of CAFs. More importantly, we underscore advances in strategies and clinical trials to target CAF in various cancers, and we also summarize progressions of CAF in cancer immunotherapy.

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Section: Background Knowledge Of Cafsmentioning

confidence: 99%

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Zhang,

Yue,

Chen

et al. 2023

Mol Cancer

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“…The toxicity of MCIEX on Hela and CT26 was detected using CCK‐8 kit and Calcein /PI Assay Kit. [ 56 ] For CCK‐8 cell viability assay, 5000 Hela or CT26 cells were seeded into 96‐well plates and grown for 24 h. Then, 100 µL medium including MCIEX, DOX or MCIEX‐DOX was added into each well. As the drug loading rate of MCIEX‐DOX was ≈10 wt%, the weight of MCIEX‐DOX used was set as ten times that of DOX.…”

Section: Methodsmentioning

confidence: 99%

Weak Ion‐Exchange Based Magnetic Swarm for Targeted Drug Delivery and Chemotherapy

Feng,

Shen,

Chen

et al. 2023

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Swimming microrobots that are actuated by multiple stimuli/fields display various intriguing collective behaviors, ranging from phase separation to clustering and giant number fluctuation; however, it is still chanllenging to achieve multiple responses and functionalities within one colloidal system to emulate high environmental adaptability and improved tasking capability of natural swarms. In this work, a weak ion‐exchange based swarm is presented that can self‐organize and reconfigure by chemical, light, and magnetic fields, showing living crystal, amorphous glass, liquid, chain, and wheel‐like structures. By changing the frequency and strength of the rotating magnetic field, various well‐controlled and fast transformations are obtained. Experiments show the high adaptability and functionality of the microrobot swarm in delivering drugs in confined spaces, such as narrow channels with turns or obstacles. The drug‐carrying swarm exhibits excellent chemtherapy for Hela and CT26 cells due to the pH‐enhanced drug release and locomotion. This reconfigurable microswarm provides a new platform for biomedical and environmental applications.

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“…More than simple elimination of CAFs, the nanoemulsion prepared by Chungen Xing et al can simultaneously deliver doxorubicin that can induce the apoptosis of CAFs, and siRNA‐targeting hepatocyte growth factors (HGF) so as to inhibit the chemotherapy‐induced surge of HGF mRNA, which may stimulate tumor proliferation and CAF reproduction. [ 121 ]…”

Section: Methods To Reconstruct Tmementioning

confidence: 99%

“…More than simple elimination of CAFs, the nanoemulsion prepared by Chungen Xing et al can simultaneously deliver doxorubicin that can induce the apoptosis of CAFs, and siRNA-targeting hepatocyte growth factors (HGF) so as to inhibit the chemotherapy-induced surge of HGF mRNA, which may stimulate tumor proliferation and CAF reproduction. [121] From another perspective, destroying tumor stroma is not the necessary condition to break through the isolation of TME. Instead, there has been some progress in decorating certain groups on nanoparticles to penetrate into ECM.…”

Section: Remove Physical Barriersmentioning

confidence: 99%

Enhancing the Treating Efficacy of Immunotherapy through the Restructure of Tumor Microenvironment

Gong,

Jia,

Zhou

et al. 2023

Advanced NanoBiomed Research

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The therapeutic modes of cancers have been profoundly renovated by immunotherapies, which have shown extraordinary treating efficacy in certain tumor entities. However, the majority of cancer patients have not profited from it because of the negative effects of tumor microenvironment (TME) on human innate and/or adaptive immunity, including hypoxia, acidification, irregular vasculature, and a plethora of immunosuppressive cells and small molecules, which contribute to tumor progression, migration, resistance to drug, and so forth. Accordingly, it is feasible to enhance the efficacy of immunotherapies and increase the patients’ survival through the restructure of TME. Herein, the mechanisms and reverberations of aforementioned immunosuppressive elements are concentrated on, and latest therapeutic achievements and combined technologies that have been demonstrated effective in boosting immunotherapies by TME modulation are enumerated.

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Cancer-associated fibroblast-targeted nanodrugs reshape colorectal tumor microenvironments to suppress tumor proliferation, metastasis and improve drug penetration

Abstract: Cancer-associated fibroblasts (CAFs) produce a critical tumor-promoting effect by cellular crosstalk with cancer cells and remodel the extracellular matrix (ECM) to form a protective physical barrier. The simple elimination of...

Cited by 13 publications

References 44 publications

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Weak Ion‐Exchange Based Magnetic Swarm for Targeted Drug Delivery and Chemotherapy

Enhancing the Treating Efficacy of Immunotherapy through the Restructure of Tumor Microenvironment

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