Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis

Lv, Yaqi; Zhao, Xin; Zhu, Lifei; Li, Sijia; Xiao, Qingqing; He, Wei; Yin, Lifang

doi:10.7150/thno.23209

Cited by 67 publications

(50 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other side, we found that the inhibition efficacy in metastasis from nanoparticle formulation was markedly different from that of the free drug, despite that their discrepancy of MMP inhibition in vivo was less than 20% (Figure ) . In this study, MATT‐LTSLs enabled threefold of metastasic nodules less than the free MATT (Figure c,d), being in line with our previous reports . Therefore, we speculate that abundant MMPs exist in the tumor site; and as a result, effective delivery of MATT to the tumor site with carriers is indispensable.…”

Section: Discussionsupporting

confidence: 89%

“…Surprisingly, recent studies unveiled that the drug could inhibit the metastasis, alleviate the inflammation, and regulate the immune system via inhibition of MMPs. Indeed, our previous reports indicated the drug blocked the metastasis significantly . On the other side, we found that the inhibition efficacy in metastasis from nanoparticle formulation was markedly different from that of the free drug, despite that their discrepancy of MMP inhibition in vivo was less than 20% (Figure ) .…”

Section: Discussionmentioning

confidence: 59%

“…After that, the exploitation of the drug was terminated. Surprisingly, recent studies unveiled that the drug could inhibit the metastasis, alleviate the inflammation, and regulate the immune system via inhibition of MMPs. Indeed, our previous reports indicated the drug blocked the metastasis significantly .…”

Section: Discussionmentioning

confidence: 99%

“…In our previous reports, we had demonstrated well that marimastat (MATT) was able to inhibit the MMPs and the resulted metastasis effectively via mimicking the substrate of the MMPs to work with MMPs in a competitive and reversible pattern . MATT is of low toxicity toward cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…However, its combined use with cytotoxicity agents, for example, paclitaxel (PTX) which is a potent antitumor drug acting via targeting the tubulin, can compensate the drawback and treat metastatic cancer. Previously by assembling prodrug polymer‐PTX and MATT‐loaded nanoparticles, coloaded nanocomplexes were designed to treat metastatic cancer in a 4T1 tumor‐bearing model . Although effective antitumor efficacy was demonstrated, the preparation of such complexes was too complicated to be characterized and to achieve the clinical transition.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

“Locked” cancer cells are more sensitive to chemotherapy

Lyu

Xiao

et al. 2019

Bioengineering & Transla Med

Self Cite

View full text Add to dashboard Cite

The treatment of metastatic cancer is a great challenging issue throughout the world. Conventional chemotherapy can kill the cancer cells and, whereas, would exacerbate the metastasis and induce drug resistance. Here, a new combinatorial treatment strategy of metastatic cancer was probed via subsequentially dosing dual nanomedicines, marimastat‐loaded thermosensitive liposomes (MATT‐LTSLs) and paclitaxel nanocrystals (PTX‐Ns), via intravenous and intratumoral injection. First, the metastasis was blocked and cancer cells were locked in the tumor microenvironment (TME) by delivering the matrix metalloproteinase (MMP) inhibitor, MATT, to the tumor with LTSLs, downregulating the MMPs by threefold and reducing the degradation of the extracellular matrix. And then, the “locked” cancer cells were efficiently killed via intratumoral injection of the other cytotoxic nanomedicine, PTX‐Ns, along with no metastasis and 100% inhibition of tumor growth. This work highlights the importance of the TME's integrity in the chemotherapy duration. We believe this is a generalized strategy for cancer treatment and has potential guidance for the clinical administration.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

“Locked” cancer cells are more sensitive to chemotherapy

Lyu

Xiao

et al. 2019

Bioengineering & Transla Med

Self Cite

View full text Add to dashboard Cite

show abstract

Metallodrugs: an approach against invasion and metastasis in cancer treatment

2022

View full text Add to dashboard Cite

Cancer is a heterogeneous and multifactorial disease that causes high mortality throughout the world; therefore, finding the most effective therapies is a major research challenge. Currently, most anticancer drugs present a limited number of well‐established targets, such as cell proliferation or death; however, it is important to consider that the worse progression of cancer toward pathological stages implies invasion and metastasis processes. Medicinal Inorganic Chemistry (MIC) is a young area that deals with the design, synthesis, characterization, preclinical evaluation, and mechanism of action of new inorganic compounds, called metallodrugs. The properties of metallic ions allow enriching of strategies for the design of new drugs, enabling the adjustment of physicochemical and stereochemical properties. Metallodrugs can adopt geometries, such as tetrahedral, octahedral, square planar, and square planar pyramid, which adjusts their arrangement and facilitates binding with a wide variety of targets. The redox properties of some metal ions can be modulated by the presence of the bound ligands to adjust their interaction, thereby opening a range of mechanisms of action. In this regard, the mechanisms of action that trigger the biological activity of metallodrugs have been generally identified by: (a) coordination of the metal to biomolecules (for instance, cisplatin binds to the N7 in DNA guanine, as Pt‐N via coordination of the inhibition of enzymes); (b) redox‐active; and (c) ROS production. For this reason, a series of metallodrugs can interact with several specific targets in the anti‐invasive processes of cancer and can prevent metastasis. The structural base of several metal compounds shows great anticancer potential by inhibiting the signaling pathways related to cancer progression. In this minireview, we present the advances in the field of antimetastatic effects of metallodrugs.

show abstract

Multi‐Domain Photopatterned 3D Tumor Constructs in a Micro‐Physiological System for Analysis, Quantification, and Isolation of Infiltrating Cells

2020

View full text Add to dashboard Cite

of metastasis involves multiple steps, [2] including movement of tumor cells into adjacent tissues, migration through the endothelium into blood vessels or lymphatics (intravasation), passage via circulation, and extravasation to and proliferation in distant tissue. However, the factors that contribute to this complex cascade of events are poorly understood; thus, there is a need for improved model systems to investigate them. Even the initial stage of metastasis, in which cancer cells infiltrate locally into adjacent tissue, is difficult to study in vitro because available technologies represent the in vivo environment poorly and have characteristics that may be practically or experimentally restrictive. For example, established techniques [3] like the classical transwell migration assay [4] and scratch assay [5] have proven to be valuable for probing chemotaxis and wound healing potential, respectively, however, they feature 2D cell cultures that do not reflect the 3D nature of tissues in which cancer cells reside and require large amounts of cells. Additionally, many conventional assays typically do not allow for the real-time assessment of cell viability; a capacity that is especially critical for studying the effects of therapeutic agents that may target metastasis. Cancer cell motility plays a central role in metastasis and tumor invasion butcan be difficult to study accurately in vitro. A simple approach to address this challenge through the production of monolithic, photopatterned 3D tumor constructs in situ in a microfluidic device is described here. Through stepwise fabrication of adjoining hydrogel regions with and without incorporated cells, multidomain structures with defined boundaries are produced. By imaging cells over time, cellular activity with arbitrary control over medium conditions, including drug concentration and flow rate, is studied. First, malignant human colon carcinoma cells (HCT116) are studied for 10 days, comparing invasion dynamics and viability of cells in normal media to those exposed to two independent chemotherapeutic drugs: anti-proliferative 5-fluorouracil and anti-migratory Marimastat. Cytotoxicity is measured and significant differences are observed in cellular dynamics (migrating cell count, distance traveled, and rate) that correlate with the mechanism of each drug. Then, the platform is applied to the selective isolation of infiltrated cells through the photopatterning and subsequent dissolution of cleavable hydrogel domains. As a demonstration, the preferential collection of highly migratory cells (HCT116) over a comparable cell line with low malignancy and migratory potential (Caco-2) is shown.

show abstract

Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis

Cited by 67 publications

References 31 publications

“Locked” cancer cells are more sensitive to chemotherapy

“Locked” cancer cells are more sensitive to chemotherapy

Metallodrugs: an approach against invasion and metastasis in cancer treatment

Multi‐Domain Photopatterned 3D Tumor Constructs in a Micro‐Physiological System for Analysis, Quantification, and Isolation of Infiltrating Cells

Contact Info

Product

Resources

About