Integrin-Mediated Delivery of Drugs and Nucleic Acids for Anti-Angiogenic Cancer Therapy: Current Landscape and Remaining Challenges

Majumder, Poulami

doi:10.3390/bioengineering5040076

Cited by 20 publications

(14 citation statements)

References 129 publications

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“…Additionally, integrin receptors are overexpressed in tumor ECs and play a key role connecting the cell cytoskeleton to the extracellular matrix protein ligands such as arginine-glycine-aspartic acid (RGD). This binding interaction between integrin and protein ligands is an important mechanism during the angiogenesis of tumor endothelial cells (52).…”

Section: Cancer and Angiogenesismentioning

confidence: 99%

Role of Matrix Metalloproteinases in Angiogenesis and Cancer

et al. 2019

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During angiogenesis, new vessels emerge from existing endothelial lined vessels to promote the degradation of the vascular basement membrane and remodel the extracellular matrix (ECM), followed by endothelial cell migration, and proliferation and the new generation of matrix components. Matrix metalloproteinases (MMPs) participate in the disruption, tumor neovascularization, and subsequent metastasis while tissue inhibitors of metalloproteinases (TIMPs) downregulate the activity of these MMPs. Then, the angiogenic response can be directly or indirectly mediated by MMPs through the modulation of the balance between pro-and anti-angiogenic factors. This review analyzes recent knowledge on MMPs and their participation in angiogenesis.

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Section: Cancer and Angiogenesismentioning

confidence: 99%

Role of Matrix Metalloproteinases in Angiogenesis and Cancer

et al. 2019

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“…It participates in activation and migration of endothelial cells, mediates endothelial cell proliferation and inhibits endothelial cell apoptosis, thus promoting angiogenesis 23-25. Integrin can also participate in the transformation, growth, invasion, metastasis and apoptosis of cancer cells by transmitting specific signals or inducing gene expression 26,27. Xu, H.M. et al found that ES-2 had good anti-angiogenetic activity in vitro , but its activity in vivo was moderated 28.…”

Section: Discussionmentioning

confidence: 99%

Anti-Tumor Activity and Pharmacokinetics of AP25-Fc Fusion Protein

Pei

Chun-ming

et al. 2019

Int. J. Med. Sci.

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AP25 is an anti-tumor peptide with a high affinity for integrins. It exerts its anti-tumor activity by inhibiting angiogenesis and by directly inhibiting the growth of tumor cells. Its half-life time in vivo is only about 50 minutes, which limits its clinical application. In order to prolong the half-life time of AP25 while preserving its anti-tumor activity, several fusion proteins of AP25 and IgG4 Fc were designed and expressed; their anti-tumor activity and pharmacokinetics properties were evaluated. Firstly, four AP25-Fc fusion protein sequences were designed, and the corresponding proteins were expressed and purified. Based on the results of HUVEC migration inhibition assay, HUVEC and tumor cell proliferation inhibition assay and yields of expression by HEK293 cells, the fusion protein designated PSG4R was selected for further evaluation. The anti-tumor effect of PSG4R was then evaluated in vivo on HCT-116 nude mice xenograft model. And the pharmacokinetics properties of PSG4R were investigated in rats. The results showed that PSG4R could inhibit the growth of xenografts of human colon cancer cell line HCT-116 in nude mice by intravenous administration of 40 mg/kg once every two days. The half-life time of PSG4R was 56.270 ± 15.398 h. This study showed that the construction of AP25-Fc fusion protein could significantly prolong the half-life of AP25 while retaining its anti-tumor activity, which provides a new direction for new drug development of AP25.

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“…In another study, a micellar delivery vehicle decorated with an anti-angiogenic peptide has been shown to inhibit α v β 3 mediated neovascularization in endothelial cells (100). Several anti-cancer drugs have also been developed against integrin ligands or by using integrintargeted encapsulated nanoparticles as vehicles to unload drugs into the vasculature of several tumors (101).…”

Section: Integrin-targeted Therapiesmentioning

confidence: 99%

The role of integrins in inflammation and angiogenesis

2020

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Integrins are heterodimeric transmembrane cell adhesion molecules made up of alpha (α) and beta (β) subunits arranged in numerous dimeric pairings. These complexes have varying affinities to extracellular ligands. Integrins regulate cellular growth, proliferation, migration, signaling, and cytokine activation and release and thereby play important roles in cell proliferation and migration, apoptosis, tissue repair, as well as in all processes critical to inflammation, infection, and angiogenesis. This review presents current evidence from human and animal studies on integrin structure and molecular signaling, with particular emphasis on signal transduction in infants. We have included evidence from our own laboratory studies and from an extensive literature search in databases PubMed, EMBASE, Scopus, and the electronic archives of abstracts presented at the annual meetings of the Pediatric Academic Societies. To avoid bias in identification of existing studies, key words were short-listed prior to the actual search both from anecdotal experience and from PubMed’s Medical Subject Heading (MeSH) thesaurus. Impact Integrins are a family of ubiquitous αβ heterodimeric receptors that interact with numerous ligands in physiology and disease. Integrins play a key role in cell proliferation, tissue repair, inflammation, infection, and angiogenesis. This review summarizes current evidence from human and animal studies on integrin structure and molecular signaling and promising role in diseases of inflammation, infection, and angiogenesis in infants. This review shows that integrin receptors and ligands are novel therapeutic targets of clinical interest and hold promise as novel therapeutic targets in the management of several neonatal diseases.

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Integrin-Mediated Delivery of Drugs and Nucleic Acids for Anti-Angiogenic Cancer Therapy: Current Landscape and Remaining Challenges

Cited by 20 publications

References 129 publications

Role of Matrix Metalloproteinases in Angiogenesis and Cancer

Role of Matrix Metalloproteinases in Angiogenesis and Cancer

Anti-Tumor Activity and Pharmacokinetics of AP25-Fc Fusion Protein

The role of integrins in inflammation and angiogenesis

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