Towards extracellular matrix normalization for improved treatment of solid tumors

Abyaneh, Hoda Soleymani; Regenold, Maximilian; McKee, Trevor D.; Allen, Christine; Gauthier, Marc A.

doi:10.7150/thno.39995

Cited by 75 publications

(60 citation statements)

References 183 publications

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“…Extracellular matrix (ECM) is composed of protein and carbohydrates, with the functions of connection, support, water retention, anti-stress and protection. ECM supports the basic life activities of cells, such as proliferation, differentiation, and migration [92,93]. However, tumors are often accompanied by dysfunction of ECM.…”

Section: Reshaping Ecm To Promote Tumor Progressionmentioning

confidence: 99%

Exosomal miRNAs in tumor microenvironment

Tan

Xia

et al. 2020

J Exp Clin Cancer Res

127

117

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Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.

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Section: Reshaping Ecm To Promote Tumor Progressionmentioning

confidence: 99%

Exosomal miRNAs in tumor microenvironment

Tan

Xia

et al. 2020

J Exp Clin Cancer Res

127

117

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“…Compared with the normal group, the DOX-PCL-PEG-COOH, DOX-PCL-PEG-ColIV, and DOX-PCL-PEG-ColIV/CLU nanoparticle groups showed no obvious histological changes in the main organs, including the heart, liver, spleen, lung, and kidney, during the treatment. Although DOX-PCL-PEG-ColIV nanoparticles showed distributed in some organs in Figure 6 A and B, no obvious toxicity resulted from the treatment because the nanoparticles can be accumulated in the capillary basement membranes of various organs but hardly penetrate the capillary wall through the enhanced permeability and retention effect 48 , 49 .…”

Section: Resultsmentioning

confidence: 99%

Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues

Hu¹,

Chen²,

Sun³

et al. 2021

Theranostics

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Purpose: Novel collagenase IV (ColIV) and clusterin (CLU)-modified polycaprolactone-polyethylene glycol (PCL-PEG) nanoparticles that load doxorubicin (DOX) were designed and fully evaluated in vitro and in vivo . Methods: PCL-PEG-ColIV was synthesized by linking PCL-PEG and ColIV through a carbodiimide method. DOX-loaded nanoparticles (DOX-PCL-PEG-ColIV) were self-assembly prepared, followed by noncovalently adsorbing CLU on the DOX-PCL-PEG-ColIV surface to obtain DOX-PCL-PEG-ColIV /CLU nanoparticles, which can penetrate through the tumor extracellular matrix (ECM) and inhibit phagocytosis by macrophage. The physicochemical properties of nanoparticles were characterized. The cellular uptake and antiphagocytosis ability of nanoparticles in MCF-7 tumor cells and RAW264.7 cells were investigated. The penetration ability of nanoparticles was individually evaluated in the two-dimensional (2D) and three-dimensional (3D) ECM models. The tissue distribution and antitumor effect of nanoparticles were evaluated in MCF-7 cell-bearing nude mice. Results: Compared with DOX-PCL-PEG-COOH nanoparticles, DOX-PCL-PEG-ColIV/CLU nanoparticles could effectively overcome the phagocytosis by RAW264.7 and showed excellent cellular uptake in MCF-7 cells. In addition, they showed remarkable penetration ability through the 2D and 3D ECM models. DOX-PCL-PEG-ColIV/CLU nanoparticles significantly reduced the drug distribution in the liver and spleen and enhanced the drug accumulation in tumor tissue compared with DOX-PCL-PEG-COOH or DOX-PCL-PEG-ColIV nanoparticles. DOX-PCL-PEG-ColIV/CLU nanoparticles showed remarkable antitumor effect but did not cause severe pathological damages in the main tissues, including the heart, liver, spleen, lung, and kidney. Conclusion: Novel ColIV and CLU-modified PCL-PEG nanoparticles showed excellent cellular uptake, ECM penetration, antiphagocytosis, and antitumor effects both in vitro and in vivo .

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“…In addition to the EPR effect, it is also well established that solid tumours have a dense, pathological ECM. This can contribute to the heterogeneous tissue distribution of ADC and nano-formulations and can impede a successful anti-tumour response [ 29 ]. The combination of rapidly dividing cancer cells with the production and deposition of ECM constituents such as collagen and hyaluronic acid leads to a high solid stress in tumour ECM [ 30 ].…”

Section: Vascular Endothelial Transport and Target Tissue Distribumentioning

confidence: 99%

“…The solid stress might collectively cause a collapse of blood vessels in tumours with a reduced tumour blood flow, which will further impede drug delivery [ 31 ]. Approaches for normalizing tumour ECM and vessels are based on remodeling the tumour microenvironment to have the properties of healthy tissue rather than completely destroying the ECM components [ 29 , 32 ].…”

Section: Vascular Endothelial Transport and Target Tissue Distribumentioning

confidence: 99%

Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective

Dahlgren

Lennernäs

2020

Molecules

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Increased understanding of cancer biology, pharmacology and drug delivery has provided a new framework for drug discovery and product development that relies on the unique expression of specific macromolecules (i.e., antigens) on the surface of tumour cells. This has enabled the development of anti-cancer treatments that combine the selectivity of antibodies with the efficacy of highly potent chemotherapeutic small molecules, called antibody-drug conjugates (ADCs). ADCs are composed of a cytotoxic drug covalently linked to an antibody which then selectively binds to a highly expressed antigen on a cancer cell; the conjugate is then internalized by the cell where it releases the potent cytotoxic drug and efficiently kills the tumour cell. There are, however, many challenges in the development of ADCs, mainly around optimizing the therapeutic/safety benefits. These challenges are discussed in this review; they include issues with the plasma stability and half-life of the ADC, its transport from blood into and distribution throughout the tumour compartment, cancer cell antigen expression and the ADC binding affinity to the target antigen, the cell internalization process, cleaving of the cytotoxic drug from the ADC, and the cytotoxic effect of the drug on the target cells. Finally, we present a summary of some of the experimental ADC strategies used in the treatment of hepatocellular carcinoma, from the recent literature.

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Towards extracellular matrix normalization for improved treatment of solid tumors

Cited by 75 publications

References 183 publications

Exosomal miRNAs in tumor microenvironment

Exosomal miRNAs in tumor microenvironment

Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues

Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective

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