Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy

Takara, Kazuhiro; Hatakeyama, Hiroto; Kibria, Golam; Ohga, Noritaka; Hida, Kyoko; Harashima, Hideyoshi

doi:10.1016/j.jconrel.2012.06.019

Cited by 97 publications

(74 citation statements)

References 28 publications

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“…In the present study, it had been demonstrated that lipid composition also affected the uptake efficiency of NGR-SL-C, the cytotoxicity of NGR-SL-B and the targeted delivery of NGR-SL-DiR. In the previous study (Takara et al, 2012), EPC and HSPC were applied for the preparation of rhodamine-labeled NGR-modified and NGR-modified doxorubicin (DOX), respectively. The behavior of these two liposomes was both used to prove the potential of the active targeted liposomes.…”

Section: Discussionmentioning

confidence: 79%

“…Consequently, PCs with different T m s were used to prepare NGR-modified liposomes, such as 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) (Negussie et al, 2010;Dunne et al, 2011), hydrogenated soy posphatidylcholine (HSPC) (Pastorino et al, 2003;Garde et al, 2007;Takara et al, 2012) or soy posphatidylcholine (SPC) (Luo et al, 2013). The T m s of HSPC and DPPC are determined to be at 53 and 41 C, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Lipid composition has significant effect on targeted drug delivery properties of NGR-modified liposomes

et al. 2015

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The Asn-Gly-Arg (NGR) motif has previously been demonstrated to specifically bind to CD13, which is selectively overexpressed in tumor vasculature and some tumor cells (e.g. HT1080). It was reported that NGR-modified stealth liposomes (NGR-SL) could be prepared with different lipid composition, such as 1,2-dipalmitoyl-sn-glycero-phosphatidylcholine (DPPC), hydrogenated soy posphatidylcholine (HSPC) and soy posphatidylcholine (SPC). In the present study, NGR-modified liposomes were prepared with DPPC, HSPC, SPC or the mixture of HSPC and SPC. The resultant liposomes with different lipid composition were compared in terms of cell uptake, antitumor efficacy and targeted drug delivery efficiency using HT1080 tumor model. It was found that NGR-SL composed of the mixture of HSPC and SPC was able to improve targeted drug delivery efficiency to tumor producing the most significant antitumor activity. Collectively, the NGR-modified liposomes composed of the mixture of HSPC and SPC are promising carriers for the treatment of tumor. Besides NGR ligand, lipid composition could also significantly affect the targeted delivery efficiency to the tumor.

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Lipid composition has significant effect on targeted drug delivery properties of NGR-modified liposomes

et al. 2015

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“…88) NGR motif peptides have been successfully used to deliver drugs as well as liposomes to tumor vasculature. [89][90][91][92] oku and colleagues determined that the alanineplorine-arginine-plorine-glycine (APRPG) motif peptide specifically binds to tumor angiogenic vessels and demonstrated the utility of APRPG-modified PEG liposomes. 93,94) 3.2.…”

Section: -28)mentioning

confidence: 99%

The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors

Hatakeyama

Akita

Harashima

2013

Biological & Pharmaceutical Bulletin

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415

276

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Gene and nucleic acid therapy is expected to play a major role in the next generation of agents for cancer treatment. We have recently developed a multifunctional envelope-type nano device (MEND) for use as a novel nonviral gene delivery system. The modification of polyethyleneglycol (PEG), i.e., PEGylation, is a useful method for achieving a longer circulation time for the delivery of MEND to a tumor via the enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits cellular uptake and endosomal escape, which results in significant loss of activity of the delivery system. For successful nucleic acid delivery for cancer treatment, the crucial problem associated with the use of PEG, i.e., the "PEG dilemma" must be resolved. In this review, we describe the development and applications of MEND and discuss various strategies for overcoming the PEG dilemma based on the manipulation of both pharmacokinetics and intracellular trafficking of cellular uptake and endosomal release. To increase cellular uptake, target ligands including proteins, peptides, antibodies and aptamers that recognize molecules specifically expressed on tumors are first introduced. Second, cleavable PEG systems are described. The cleavage of PEG from carriers was achieved in response to the intracellular environment as well as the tumor microenvironment, which improvs cellular uptake and endosomal escape. Then, endosomal fusogenic peptides are discussed. Finally, pH-sensitive liposomes using pH-sensitive lipids are described.

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“…The R8 functions as both a cellular uptake device via macropinocytosis and as a mitochondrial targeting peptide via electrostatic interactions with negatively charged mitochondria [17][18][19] . We also developed a dual-ligand system in which the nanocarrier is modified with a specific ligand and R8 20,21 . These systems have a synergistic effect on both selectivity and cellular uptake.…”

Section: Introductionmentioning

confidence: 99%

A Dual-Ligand Liposomal System Composed of a Cell-Penetrating Peptide and a Mitochondrial RNA Aptamer Synergistically Facilitates Cellular Uptake and Mitochondrial Targeting

Yamada

Furukawa

Harashima

2016

Journal of Pharmaceutical Sciences

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Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy

Abstract: Anti-angiogenic therapy is a potential chemotherapeutic strategy for the treatment of drug resistant cancers. However, a method for delivering such drugs to tumor endothelial cells remains to be a major impediment to the success of anti-angiogenesis therapy. We designed

Cited by 97 publications

References 28 publications

Lipid composition has significant effect on targeted drug delivery properties of NGR-modified liposomes

Lipid composition has significant effect on targeted drug delivery properties of NGR-modified liposomes

The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors

A Dual-Ligand Liposomal System Composed of a Cell-Penetrating Peptide and a Mitochondrial RNA Aptamer Synergistically Facilitates Cellular Uptake and Mitochondrial Targeting

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