Antiangiogenic photodynamic therapy (PDT) by using long-circulating liposomes modified with peptide specific to angiogenic vessels

Ichikawa, Kanae; Hikita, Tomoya; Maeda, Noriyuki; Yonezawa, Sei; Takeuchi, Yoshito; Asai, Tomohiro; Namba, Yukihiro; Oku, Naoto

doi:10.1016/j.bbamem.2005.02.003

Cited by 72 publications

(51 citation statements)

References 22 publications

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“…TPC-Ahx-ATWLPPR displayed enhanced uptake and photodynamic properties in endothelial cells compared with its nonconjugated counterpart TPC. Destruction of the neovasculature of tumors may indirectly lead to tumor eradication, following deprivation of life-sustaining nutrients and oxygen (Folkman, 1995;Dougherty et al, 1998), and this antivascular effect is thought to play a major part in the destruction of some vascularized tumors by PDT (Ichikawa et al, 2005).…”

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confidence: 99%

Metabolic Profile of a Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1: An in Vivo and in Vitro Study

Tirand¹,

Thomas²,

Dodeller³

et al. 2007

Drug Metab Dispos

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ABSTRACT:Because angiogenic endothelial cells of the tumor vasculature represent an interesting target to potentiate the antivascular effect of photodynamic therapy, we recently described the conjugation of a photosensitizer [5-(4-carboxyphenyl)-10,15,20-triphenylchlorin (TPC)], via a spacer [6-aminohexanoic acid (Ahx)], to a vascular endothelial growth factor receptor-specific heptapeptide [H-AlaThr-Trp-Leu-Pro-Pro-Arg-OH (ATWLPPR)] and showed that TPCAhx-ATWLPPR binds to neuropilin-1. Because peptides often display low stability in biological fluids, we examined the in vivo and in vitro stability of this conjugate by high-performance liquid chromatography and matrix-assisted laser desorption ionization/time of flight mass spectrometry. TPC-Ahx-ATWLPPR was stable in vitro in human and mouse plasma for at least 24 h at 37°C but, following i.v. injection in glioma-bearing nude mice, was degraded in vivo to various rates, depending on the organ considered. TPCAhx-A was identified as the main metabolic product, and biodistribution studies suggested that its appearance in plasma mainly resulted from the degradation of the peptidic moiety into organs of the reticuloendothelial system. According to in vitro cell culture experiments, TPC-Ahx-ATWLPPR was also significantly degraded after incorporation in human umbilical vein endothelial cells (HUVEC), mainly into TPC-Ahx-A and to a lesser extent into TPCAhx-AT and TPC-Ahx-ATWLPP. TPC-Ahx-ATWLPPR mostly localized into lysosomes, and when HUVEC were treated with the lysosomal enzymes' inhibitor ammonium chloride, this resulted in a significant decrease of the peptide degradation. This study provides essential information for the choice of the time of activation of the photosensitizer (drug-light interval) not to be exceeded and for the future design of more stable molecules.

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confidence: 99%

Metabolic Profile of a Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1: An in Vivo and in Vitro Study

Tirand¹,

Thomas²,

Dodeller³

et al. 2007

Drug Metab Dispos

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“…However, Photofrin can cause prolonged skin photosensitization, where patients are required to avoid direct exposure to sunlight for a period of 4 to 6 weeks. Current strategies under development include attempts to direct the photosensitizing agent to the tumor by active targeting approaches, such as peptide conjugates and antibodies (3 -7), incorporation within liposomes (8,9), and encapsulation within polymeric nanoparticles (10 -14) in an attempt to deliver higher local concentrations at the therapeutic site.…”

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confidence: 99%

Vascular Targeted Nanoparticles for Imaging and Treatment of Brain Tumors

Reddy¹,

Bhojani

McConville

et al. 2006

Clinical Cancer Research

457

343

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Purpose: Development of new therapeutic drug delivery systems is an area of significant research interest. The ability to directly target a therapeutic agent to a tumor site would minimize systemic drug exposure, thus providing the potential for increasing the therapeutic index. Experimental Design: Photodynamic therapy (PDT) involves the uptake of a sensitizer by the cancer cells followed by photoirradiation to activate the sensitizer. PDTusing Photofrin has certain disadvantages that include prolonged cutaneous photosensitization. Delivery of nanoparticles encapsulated with photodynamic agent specifically to a tumor site could potentially overcome the drawbacks of systemic therapy. In this study, we have developed a multifunctional polymeric nanoparticle consisting of a surface-localized tumor vasculature targeting F3 peptide and encapsulated PDTand imaging agents. Results:The nanoparticles specifically bound to the surface of MDA-435 cells in vitro and were internalized conferring photosensitivity to the cells. Significant magnetic resonance imaging contrast enhancement was achieved in i.c. rat 9L gliomas following i.v. nanoparticle administration. Serial magnetic resonance imaging was used for determination of pharmacokinetics and distribution of nanoparticles within the tumor. Treatment of glioma-bearing rats with targeted nanoparticles followed by PDT showed a significant improvement in survival rate when compared with animals who received PDT after administration of nontargeted nanoparticles or systemic Photofrin. Conclusions:This study reveals the versatility and efficacy of the multifunctional nanoparticle for the targeted detection and treatment of cancer.Photodynamic therapy (PDT) relies on the selective uptake of a photosensitizing molecule in a tumor relative to the surrounding normal parenchyma followed by exposure to the appropriate wavelength of light to activate the photosensitizer (1). When activated by light irradiation, the photosensitizer interacts with molecular oxygen to produce a cytotoxic, shortlived species known as singlet oxygen. PDT elicits both apoptotic and necrotic responses within treated tumors and produces microvascular injury leading to inflammation and hypoxia. Photofrin, a complex mixture of porphyrin oligomers, is one of the most efficient photosensitizers approved for PDT of cancer (2). However, Photofrin can cause prolonged skin photosensitization, where patients are required to avoid direct exposure to sunlight for a period of 4 to 6 weeks. Current strategies under development include attempts to direct the photosensitizing agent to the tumor by active targeting approaches, such as peptide conjugates and antibodies (3 -7), incorporation within liposomes (8, 9), and encapsulation within polymeric nanoparticles (10 -14) in an attempt to deliver higher local concentrations at the therapeutic site.A recent report of a sub-100 nm dynamic nanoparticle platform composed of polyacrylamide, which could be loaded with a photoactivatable agent (methylene blue) for the spe...

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“…1A). In contrast, BPD-MA in APRPG-PEG-modified liposomes induced drastic tumor regression compared with that obtained with PEGylated liposomes after irradiation of laser given 3 h after injection of the liposomes 42) (Fig. 1B).…”

Section: Introductionmentioning

confidence: 84%

“…For this purpose, laser irradiation was performed early after the injection of liposomal BPD-MA 37) or liposomes modified with polycations [38][39][40] or APRPG peptides. 41,42) Interestingly, BPD-MA in PEGylated liposomes and that in APRPG-PEG-modified liposomes similarly accumulated in tumors of tumor-bearing mice 3 h after injection (Fig. 1A).…”

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 photodynamic therapy (PDT) by using long-circulating liposomes modified with peptide specific to angiogenic vessels

Cited by 72 publications

References 22 publications

Metabolic Profile of a Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1: An in Vivo and in Vitro Study

Metabolic Profile of a Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1: An in Vivo and in Vitro Study

Vascular Targeted Nanoparticles for Imaging and Treatment of Brain Tumors

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

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