Antiangiogenic cancer therapy using tumor vasculature-targeted liposomes encapsulating 3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one, SU5416

Ida, Tomoko; Asai, Tomohiro; Shimizu, Kosuke; Koizumi, Fumiaki; Maeda, Noriyuki; Baba, Kazuhiko; Oku, Naoto

doi:10.1016/j.canlet.2008.05.009

Cited by 38 publications

(23 citation statements)

References 26 publications

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“…The authors of this review encapsulated SU5416 (a VEGF receptor tyrosine kinase inhibitor) into PEGylated liposomes that had been modified to display Ala-Pro-ArgPro-Gly (APRPG) (a peptide targeting newly formed blood vessels) 48,49 and injected the liposomes intravitreally into a rat experimental model of CNV to determine whether it was possible for the CNV-targeted drug to be released inside the vitreous body (Figure 4).…”

Section: Liposomesmentioning

confidence: 99%

Liposomes and nanotechnology in drug development: focus on ocular targets

Honda¹,

Asai²,

Oku³

et al. 2013

IJN

126

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Abstract:Poor drug delivery to lesions in patients' eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood-retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/ nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases.

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Section: Liposomesmentioning

confidence: 99%

Liposomes and nanotechnology in drug development: focus on ocular targets

Honda¹,

Asai²,

Oku³

et al. 2013

IJN

126

View full text Add to dashboard Cite

show abstract

“…On the other hand, we have explored a DDS targeting angiogenic vessels in which cytotoxic drugs, [12][13][14][15][16][17][18][19][20] angiogenesis inhibitors, 21,22) and nucleic acids such as siRNA 23,24) have been delivered to angiogenic endothelial cells using targeted liposomes. Since proliferating cells are killed by cytotoxic drugs nonspecifically, not only tumor cells but also angiogenic endothelial cells should be attacked by these drugs.…”

Section: The Concept Of Angiogenic Vessel-tar-geting Ddsmentioning

confidence: 99%

“…19,22) Although angiogenesis inhibitors have a selective mechanism compared with cytotoxic drugs, the limited efficacy of these inhibitors remains a problem. To improve both selectivity and therapeutic efficacy at the same time, vascular disrupting agents (VDAs), 28) a new class of potential anticancer drugs, may be ideal for angiogenic vessel-targeting DDS.…”

Section: Prospects For Angiogenic Vessel-target-ing Ddsmentioning

confidence: 99%

Nanoparticle-Mediated Delivery of Anticancer Agents to Tumor Angiogenic Vessels

Asai

2012

Biological & Pharmaceutical Bulletin

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Nanoparticle-mediated drug delivery systems targeting tumor angiogenic vessels have been studied for antineovascular cancer therapy achieved by induction of apoptosis of angiogenic endothelial cells. Nanoparticles such as liposomes are considered to accumulate in tumors due to the enhanced permeability and retention effect. The delivery efficiency of this system appears to be affected by the density of tumor angiogenic vessels regardless of modification with tumor-targeting ligands on the surface of nanoparticles. It remains a challenging problem to deliver sufficient amounts of anticancer drugs to hypovascular tumors using nanoparticles. On the other hand, the strategy of angiogenic vessel-targeting is theoretically different from that of tumor cell-targeting since target angiogenic endothelial cells face the circulating blood. In addition, this strategy is expected to cause indirect tumor regression by disrupting angiogenic vessels. In this review, our recent studies are summarized to show the actual efficacy of angiogenic vessel-targeting delivery. We have developed various angiogenic vessel-targeted liposomes and evaluated them in experimental cancer models such as drug-resistant and hypovascular tumors. Our data indicate that increased apoptosis of angiogenic endothelial cells can be achieved by the targeted liposomes encapsulating cytotoxic drugs, resulting in enhanced anticancer effects. The advantages of angiogenic vessel-targeting are discussed based on our recent findings to provide an insight into why angiogenic vessels are a promising target for advanced cancer therapy.

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“…The eradication of neovessels by delivering anticancer drugs to the vessels would induce the cut off of the oxygen and nutrient supply to tumor cells, thus causing tumor regression; and so we designated this therapy as anti-neovascular therapy (ANET). [23][24][25][26] In this type of therapy, anticancer drugs are expected to be efficiently delivered to angiogenic endothelial cells, since such drugs contained in liposomes firstly meet blood vessels after injec- Naoto Oku tion of them into bloodstream and, thus, easily interact with them. 27,28) Lipid composition and characteristics of liposomes used for ANET and other studies described in the review are shown in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Innovations in Liposomal DDS Technology and Its Application for the Treatment of Various Diseases

Oku

2017

Biological & Pharmaceutical Bulletin

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Liposomes have been widely used as drug carriers in the field of drug delivery systems (DDS), and they are thought to be ideal nano-capsules for targeting DDS after being injected into the bloodstream. In general, DDS drugs meet the needs of aged and super-aged societies, since the administration route of drugs can be changed, the medication frequency reduced, the adverse effects of drugs suppressed, and so on. In fact, a number of liposomal drugs have been launched and used worldwide including liposomal anticancer drugs, and these drugs have appeared on the market owing to various innovations in liposomal DDS technologies. The accumulation of long-circulating liposomes in cancer tissue is driven by the enhanced permeability and retention (EPR) effect. In this review, liposome-based targeting DDS for cancer therapy is briefly discussed. Since cancer angiogenic vessels are the ideal target of drug carriers after their injection and are critical for cancer growth, damaging of these neovessels has been an approach for eradicating cancer cells. Also, the usage of liposomal DDS for the treatment of ischemic stroke is possible, since we observed that PEGylated liposomes accumulate in the site of cerebral ischemia in transient middle cerebral artery occlusion (t-MCAO) model rats. Interestingly, liposomes carrying neuroprotectants partly suppress ischemia/reperfusion injury of these model rats, suggesting that the EPR effect also works in ischemic diseases by causing an increase in the permeability of the blood vessel endothelium. The potential of liposomal DDS against life-threatening diseases might thus be attractive for supporting long-lived societies.

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Antiangiogenic cancer therapy using tumor vasculature-targeted liposomes encapsulating 3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one, SU5416

Cited by 38 publications

References 26 publications

Liposomes and nanotechnology in drug development: focus on ocular targets

Liposomes and nanotechnology in drug development: focus on ocular targets

Nanoparticle-Mediated Delivery of Anticancer Agents to Tumor Angiogenic Vessels

Innovations in Liposomal DDS Technology and Its Application for the Treatment of Various Diseases

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