Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels

Krasnici, Senat; Werner, Alexander; Eichhorn, Martin; Schmitt‐Sody, Marcus; Pahernik, Sascha; Sauer, Birgitta; Schulze, B.; Teifel, Michael; Michaelis, Uwe; Naujoks, Kurt; Dellian, Marc

doi:10.1002/ijc.11108

Cited by 268 publications

(201 citation statements)

References 27 publications

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“…administration. 5 The positive charge significantly increases the uptake of the liposomes by the endothelial cells of the blood vessels in tumor tissues 6 and this has made the cationic liposomes useful for tumor targeted drug delivery. Although cationic liposomes have been used to transfect nucleic acids in cells for several years, their application in gene therapy is limited because of the variable transfection 7,8 and systemic toxicity when injected i.v.…”

mentioning

confidence: 99%

Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo

Chien¹,

Wang²,

Carbonaro³

et al. 2004

Cancer Gene Ther

142

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Cationic liposomes have been successfully used as an alternative approach to viral systems to deliver nucleic acids. However, high toxicity and inconsistent transfection efficiency have been associated with the currently available liposomes. Therefore, a novel cationic liposome was developed based on a synthetic cationic cardiolipin analogue (CCLA) to test the DNA transfection efficiency. This CCLA-based liposome was also used to determine the therapeutic efficacy of c-raf small interfering RNA (siRNA) in mice. In this report, we showed that the CCLA-based liposome was less toxic and effectively transfected reporter genes in vitro and in vivo. The transfection efficiency in mice was seven-fold higher than the commercially available DOTAP-based liposome. In addition, craf siRNA in the presence of CCLA-based liposome induced up to 62% of growth inhibition in cancer cells. Treatment of c-raf siRNA/CCLA complex in SCID mice bearing human breast xenograft tumors resulted in 73% of tumor growth suppression as compared to free c-raf siRNA group. In conclusion, a novel CCLA-based liposome showed less toxicity and broad usage both in vitro and in vivo with DNA and siRNA.

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mentioning

confidence: 99%

Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo

Chien¹,

Wang²,

Carbonaro³

et al. 2004

Cancer Gene Ther

142

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“…5,6 These lipid complexes therefore appeared to be promising drug carriers directing chemotherapeutic compounds to the tumor endothelium to realize vascular targeting tumor therapy. 15,16 This novel therapeutic strategy was first realized by the synthesis of EndoTAG TM -1 (formerly known as Lipopac/MBT-0206) comprising paclitaxel encapsulated in cationic lipid complexes.…”

Section: Discussionmentioning

confidence: 99%

“…This observation is consistent with results obtained in A-MEL-3 melanomas and LLC-1 carcinomas following systemic injection of EndoTAG TM -1 or camptothecin encapsulated in cationic lipid complexes, respectively. Although several different studies have proven the charge depended tumor vascular targeting effect of cationic liposomes, 5,6,21 only a small number of investigations have addressed the important question, to which tumor compartment the encapsulated drug is delivered. By intravital microscopic analysis of Oregon Green 488 paclitaxel encapsulated in cationic liposomes we now can clearly demonstrate that paclitaxel when loaded in cationic liposomes is delivered preferentially to the tumor endothelium.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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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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“…These include the interaction of the particles with the microvascular endothelium, their extravasation and intracellular uptake into individual tumour cells (Tada et al, 2007). Of interest, these processes have been shown to be particularly dependent on the size of the used particles (Kawai et al, 2009), their charge (Krasnici et al, 2003) and the local tissue temperature (Gaber et al, 1996;Liu et al, 2004), which should be considered for the development of novel drug delivery systems exhibiting improved pharmacokinetics and anti-tumour activity.…”

Section: Drug Delivery Systemsmentioning

confidence: 99%

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

Laschke

Vollmar²,

Menger³

2011

eCM

141

125

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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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Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels

Cited by 268 publications

References 27 publications

Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo

Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery 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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