Tumor‐selective vessel occlusions by platelets after vascular targeting chemotherapy using paclitaxel encapsulated in cationic liposomes

Strieth, Sebastian; Nußbaum, Claudia; Eichhorn, Martin; Fuhrmann, Martin; Teifel, Michael; Michaelis, Uwe; Berghaus, Alexander; Dellian, Marc

doi:10.1002/ijc.23088

Cited by 53 publications

(41 citation statements)

References 30 publications

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“…The proliferation of endothelial cell plays a key role in tumor angiogenesis. For this reason, many studies have focused on antiangiogenesis or target endothelial cell receptors, such as paclitaxel encapsulated in cationic liposomes (28)(29)(30)(31)(32)(33). Paclitaxel encapsulated in cationic liposomes significantly inhibits tumor growth by a significant reduction of functional tumor microcirculation and induction of endothelial cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic Activity of Sterically Stabilized Liposomes Containing Paclitaxel (SSL-PTX): In Vitro and In Vivo

et al. 2010

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Abstract. The purpose of this present study was to evaluate the antiangiogenic activity of sterically stabilized liposomes containing paclitaxel (SSL-PTX). The SSL-PTX was prepared by the thin-film method. The release of paclitaxel from SSL-PTX was analyzed using a dialysis method. The effect of SSL-PTX on endothelial cell proliferation and migration was investigated in vitro. The antitumor and antiangiogenic activity of SSL-PTX was evaluated in MDA-MB-231 tumor xenograft growth in BALB/c nude mice. The release of paclitaxel from SSL-PTX was 22% within 24 h. Our in vitro results indicated that SSL-PTX could effectively inhibit the endothelial cell proliferation and migration at a concentrationdependent manner. We also observed that metronomic SSL-PTX induced marked tumor growth inhibition in MDA-MB-231 xenograft model via the antiangiogenic mechanism, unlike that in paclitaxel injection (Taxol) formulated in Cremophor EL (CrEL). Overall, our results suggested that metronomic chemotherapy with low-dose, CrEL-free SSL-PTX should be feasible and effective.

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Section: Discussionmentioning

confidence: 99%

Antiangiogenic Activity of Sterically Stabilized Liposomes Containing Paclitaxel (SSL-PTX): In Vitro and In Vivo

et al. 2010

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“…Moreover, tumor endothelial cell apoptosis and intratumoral thrombosis induced by EndoTAG TM -1 therapy indeed supported vascular targeting as the underlying mechanism. 17,18 In addition to paclitaxel, doxorubin, 5-FU and camptothecin have, meanwhile, been successfully encapsulated in cationic lipid complexes to realize vascular targeting therapy in preclinical animal models. 9,19,20 However, the clinical success of vascular targeting and antiangiogenic agents depends upon potential combination with conventional therapies.…”

Section: Discussionmentioning

confidence: 99%

Vascular targeting by EndoTAG™‐1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer

Eichhorn

Ischenko²,

Luedemann³

et al. 2009

Intl Journal of Cancer

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Cationic lipid complexed paclitaxel (EndoTAG TM -1) is a novel vascular targeting agent for the treatment of cancer. Here, the aim was to investigate intratumoral drug distribution after EndoTAG TM -1 therapy and analyze the impact of EndoTAG TM -1 scheduling on antitumoral efficacy. The therapeutic effect of EndoTAG TM -1 in combination with conventional gemcitabine or cisplatin therapy was evaluated in L3.6pl orthotopic pancreatic cancer and a subcutaneous Lewis lung (LLC-1) carcinoma model. Oregon Green paclitaxel encapsulated in cationic liposomes in combination with intravital fluorescence microscopy clearly exhibited delivery of the drug by EndoTAG TM -1 to the tumor endothelium, whereas Oregon Green paclitaxel dissolved in cremophor displayed an interstitial distribution pattern. The therapeutic efficacy of EndoTAG TM -1 was critically dependent on the application schedule with best therapeutic results using a metronomic rather than a maximum tolerated dose application sequence. The combination of EndoTAG TM -1 therapy and cytotoxic chemotherapy significantly enhanced antitumoral efficacy in both tumor models. Interestingly, only EndoTAG TM -1 in combination with gemcitabine was able to inhibit the incidence of metastasis in pancreatic cancer. In conclusion, vascular targeting tumor therapy by EndoTAG TM -1 combined with standard small molecular chemotherapy results in markedly enhanced antitumoral efficacy. Therefore, this combination represents a promising novel strategy for clinical cancer therapy.Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, is fundamental in tumor growth, progression and metastasis. 1 The complex network of tumor blood microvessels guarantees an adequate supply of tumor cells with nutrients and oxygen and provides efficient drainage of metabolites.Therapeutic strategies that target and disrupt already formed vessel networks of growing tumors are therefore actively pursued. In contrast with the antiangiogenesis approach, the aim of vascular targeting is to destroy the established tumor vasculature thus causing a rapid and extensive decrease in tumor blood flow, followed by secondary tumor cell death. 2,3 Ligand-directed vascular targeting agents and small molecular tubulin-binding agents have been successfully developed to induce a vascular shutdown of tumor microvessels. 4 In addition to these compounds, drug delivery systems are of considerable interest in realizing such a new therapeutic concept: cationic lipid complexes have been described to target angiogenic endothelial cells in tumor preferentially. [5][6][7] This property potentially enables selective delivery of cytotoxic drugs to tumor endothelial cells and thus vascular targeting chemotherapy. We have previously shown that vascular targeting therapy can be realized by paclitaxel or camptothecin encapsulated in cationic lipid complexes. 8,9 Treatment with these liposomal compounds significantly retarded primary tumor growth and delayed metastatic disease by an antivascular...

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“…In addition, individual necrotic cell death can be detected by the use of propidium-iodide (Harris et al, 1997), whereas apoptotic cells can be identifi ed by nuclear condensation, margination and fragmentation following local bisbenzimide staining (Vollmar et al, 2001). Besides conventional epi-illumination fl uorescence microscopy, imaging in the dorsal skinfold chamber model has increasingly been performed in recent years by means of confocal microscopy techniques (Isaka et al, 2004;Makale, 2007;Strieth et al, 2008). Using a pinhole aperture for point illumination, single-photon laser-scanning microscopy allows the detection of light from a specifi c volume within the plane of focus, so that the resultant image is comparatively free of scattered light and attendant blurring (Makale, 2007).…”

Section: Mw Laschke Et Almentioning

confidence: 99%

The dorsal skinfold chamber: window into the dynamic interaction of biomaterials with their surrounding host tissue

Laschke

Vollmar²,

Menger³

2011

eCM

146

128

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The implantation of biomaterials into the human body has become an indispensable part of almost all fi elds of modern medicine. Accordingly, there is an increasing need for appropriate approaches, which can be used to evaluate the suitability of different biomaterials for distinct clinical indications. The dorsal skinfold chamber is a sophisticated experimental model, which has been proven to be extremely valuable for the systematic in vivo analysis of the dynamic interaction of small biomaterial implants with the surrounding host tissue in rats, hamsters and mice. By means of intravital fl uorescence microscopy, this chronic model allows for repeated analyses of various cellular, molecular and microvascular mechanisms, which are involved in the early infl ammatory and angiogenic host tissue response to biomaterials during the initial 2-3 weeks after implantation. Therefore, the dorsal skinfold chamber has been broadly used during the last two decades to assess the in vivo performance of prosthetic vascular grafts, metallic implants, surgical meshes, bone substitutes, scaffolds for tissue engineering, as well as for locally or systemically applied drug delivery systems. These studies have contributed to identify basic material properties determining the biocompatibility of the implants and vascular ingrowth into their surface or internal structures. Thus, the dorsal skinfold chamber model does not only provide deep insights into the complex interactions of biomaterials with the surrounding soft tissues of the host but also represents an important tool for the future development of novel biomaterials aiming at an optimisation of their biofunctionality in clinical practice.

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Tumor‐selective vessel occlusions by platelets after vascular targeting chemotherapy using paclitaxel encapsulated in cationic liposomes

Cited by 53 publications

References 30 publications

Antiangiogenic Activity of Sterically Stabilized Liposomes Containing Paclitaxel (SSL-PTX): In Vitro and In Vivo

Antiangiogenic Activity of Sterically Stabilized Liposomes Containing Paclitaxel (SSL-PTX): In Vitro and In Vivo

Vascular targeting by EndoTAG™‐1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer

The dorsal skinfold chamber: window into the dynamic interaction of biomaterials with their surrounding host tissue

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