Chemokine‐derived peptides as carriers for gene delivery to CXCR4 expressing cells

Egorova, Anna; Kiselev, Anton; Häkli, Marika; Ruponen, Marika; Baranov, V. S.; Urtti, Arto

doi:10.1002/jgm.1366

Cited by 33 publications

(24 citation statements)

References 24 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…31,38 Other CXCR4 ligands previously investigated for targeted drug delivery showed very low or null penetration, even revealing themselves as agonists of CXCR4 and stimulating cell division. 39 In contrast, in our hands, T22-exposed cells never showed significant proliferation compared with controls (data not shown). The efficient endosomal escape of the constructs generated might be due to the proton-sponge activity of the accompanying polyhistidines that, while useful for one-step protein purification, act also as a proton sponge, permitting endosomal disruption and delivery of the functionalized materials into the cytoplasm.…”

Section: Discussioncontrasting

confidence: 67%

Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles

Unzueta¹,

Céspedes²,

Ferrer-Miralles³

et al. 2012

IJN

View full text Add to dashboard Cite

Background: Cell-targeting peptides or proteins are appealing tools in nanomedicine and innovative medicines because they increase the local drug concentration and reduce potential side effects. CXC chemokine receptor 4 (CXCR4) is a cell surface marker associated with several severe human pathologies, including colorectal cancer, for which intracellular targeting agents are currently missing. Results: Four different peptides that bind CXCR4 were tested for their ability to internalize a green fluorescent protein-based reporter nanoparticle into CXCR4 + cells. Among them, only the 18 mer peptide T22, an engineered segment derivative of polyphemusin II from the horseshoe crab, efficiently penetrated target cells via a rapid, receptor-specific endosomal route. This resulted in accumulation of the reporter nanoparticle in a fully fluorescent and stable form in the perinuclear region of the target cells, without toxicity either in cell culture or in an in vivo model of metastatic colorectal cancer. Conclusion: Given the urgent demand for targeting agents in the research, diagnosis, and treatment of CXCR4-linked diseases, including colorectal cancer and human immunodeficiency virus infection, T22 appears to be a promising tag for the intracellular delivery of protein drugs, nanoparticles, and imaging agents.

show abstract

Section: Discussioncontrasting

confidence: 67%

Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles

Unzueta¹,

Céspedes²,

Ferrer-Miralles³

et al. 2012

IJN

View full text Add to dashboard Cite

show abstract

“…Chemokine networks are thus an important emerging target for development of novel drug delivery strategies (25). By devising systems capable of simultaneous CXCR4 inhibition and delivery of antitumor agents, it should be possible to improve the overall anticancer activity (26). As part of our long-term efforts to develop dually functioning polycations for combination drug/gene delivery (27, 28), we have recently reported synthesis of polycations based on a bicyclam CXCR4 antagonist Plerixafor (PAMD) (29, 30).…”

Section: Introductionmentioning

confidence: 99%

Polymeric Plerixafor: Effect of PEGylation on CXCR4 Antagonism, Cancer Cell Invasion, and DNA Transfection

Wang

Oupický

2014

Pharm Res

View full text Add to dashboard Cite

Purpose To determine the effect of PEG modification on pharmacologic and gene delivery properties of polymeric CXCR4 antagonist based on Plerixafor. Methods Polymeric Plerixafor (PAMD) was synthesized from Plerixafor (AMD3100) and grafted with different amounts of PEG (2 kDa). CXCR4 antagonism of the synthesized polymers was determined using receptor redistribution assay. Inhibition of cancer cell invasion by the polyplexes of the synthesized polymers was assessed using Boyden-chamber method. Transfection activity of DNA polyplexes formed with the synthesized polymers was evaluated in U2OS osteosarcoma and B16F10 melanoma cells. Results Our results demonstrate that modification of PAMD with PEG decreased toxicity of the polymers, while preserving their CXCR4 antagonism. Polyplexes prepared with PEG-PAMD inhibited invasion of cancer cells to an extent similar to the commercial CXCR4 antagonist Plerixafor. Negative effect of PEG on transfection activity of PEG-PAMD polyplexes could be overcome by using polyplexes formulated with a mixture of PAMD and PEG-PAMD. Conclusion Modification of PAMD with PEG is a viable strategy to preserve the desirable CXCR4 antagonism and ability to inhibit cancer cell invasion of PAMD, while improving safety and colloidal stability of the PAMD polyplexes.

show abstract

“…Egorova et al have developed chemokine-derived peptides as carriers for gene delivery (Egorova et al 2009). The authors used three synthetic peptides for CXCR4 receptor targeting: two derived from N-terminal sequence of CXCL12 and one from viral macrophage inflammatory protein (vMIP)-II.…”

Section: Cxcr4 As Target For Ligand-mediated Delivery and Imagingmentioning

confidence: 99%

“…CXCR4/CXCL12 axis is an important emerging target for developing novel delivery strategies for improved cancer therapies (Guo et al 2014; Egorova et al 2009). In addition to utilizing CXCR4 overexpression as a simple target for improved ligand-mediated delivery of drugs to tumors, blocking CXCR4/CXCL12 interaction using CXCR4 antagonists or silencing CXCR4 expression by siRNA has potential to prevent primary tumor growth and reduce metastasis, especially when combined with chemotherapy and radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Potential of CXCR4/CXCL12 Chemokine Axis in Cancer Drug Delivery

2016

View full text Add to dashboard Cite

This review discusses the potential of CXCR4 chemokine receptor in the design of anticancer and antimetastatic drug delivery systems. The role of CXCR4 in cancer progression and metastasis is discussed in the context of the development of several types of drug delivery strategies. Overview of drug delivery systems targeted to cancers that overexpress CXCR4 is provided, together with the main types of CXCR4-binding ligands used in targeting applications. Drug delivery applications that take advantage of CXCR4 inhibition to achieve enhanced anticancer and antimetastatic activity of combination treatments are also discussed.

show abstract

Chemokine‐derived peptides as carriers for gene delivery to CXCR4 expressing cells

Abstract: The small, bifunctional peptides reported in the present study may be useful in gene delivery to (and gene therapy of) the different tumors and other cells expressing CXCR4.

Cited by 33 publications

References 24 publications

Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles

Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles

Polymeric Plerixafor: Effect of PEGylation on CXCR4 Antagonism, Cancer Cell Invasion, and DNA Transfection

Potential of CXCR4/CXCL12 Chemokine Axis in Cancer Drug Delivery

Contact Info

Product

Resources

About