PEGylation of Liposome Decreases the Susceptibility of Liposomal Drug in Cancer Photodynamic Therapy

Ichikawa, Kanae; Hikita, Tomoya; Maeda, Noriyuki; Takeuchi, Yoshito; Namba, Yukihiro; Oku, Naoto

doi:10.1248/bpb.27.443

Cited by 37 publications

(14 citation statements)

References 6 publications

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“…Of particular interest are polyethylene glycol (PEG) groups, which can be used as delivery vehicles 12-14 or may be covalently attached to Pcs 15-17 for improved delivery to target tissues. The pegylation of photosensitizers has been shown to increase their water-solubility, serum life and tumor accumulation, while reducing their uptake by the reticuloendothelial system 18-23. On the other hand, positively charged photosensitizers are of particular interest for PDT 24-31 and for photoinactivation of virus and bacteria 32-34, because of their potential stronger interactions with negatively charged cell membranes and targeted biomolecules (e.g.…”

Section: Introductionmentioning

confidence: 99%

Syntheses and Photodynamic Activity of Pegylated Cationic Zn(II)-Phthalocyanines in HEp2 Cells

Ongarora¹,

Hu²,

Verberne-Sutton³

et al. 2012

Theranostics

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Di-cationic Zn(II)-phthalocyanines (ZnPcs) are promising photosensitizers for the photodynamic therapy (PDT) of cancers and for photoinactivation of viruses and bacteria. Pegylation of photosensitizers in general enhances their water-solubility and tumor cell accumulation. A series of pegylated di-cationic ZnPcs were synthesized from conjugation of a low molecular weight PEG group to a pre-formed Pc macrocycle, or by mixed condensation involving a pegylated phthalonitrile. All pegylated ZnPcs were highly soluble in polar organic solvents but were insoluble in water; they have intense Q absorptions centered at 680 nm and fluorescence quantum yields of ca. 0.2 in DMF. The non-pegylated di-cationic ZnPc 6a formed large aggregates, which were visualized by atomic force microscopy. The cytotoxicity, cellular uptake and subcellular distribution of all cationic ZnPcs were investigated in human carcinoma HEp2 cells. The most phototoxic compounds were found to be the α-substituted Pcs. Among these, Pcs 4a and 16a were the most effective (IC50 ca. 10 μM at 1.5 J/cm2), in part due to the presence of a PEG group and the two positive charges in close proximity (separated by an ethylene group) in these macrocycles. The β-substituted ZcPcs 6b and 4b accumulated the most within HEp2 cells but had low photocytoxicity (IC50 > 100 μM at 1.5 J/cm2), possibly as a result of their lower electron density of the ring and more extended conformations compared with the α-substituted Pcs. The results show that the charge distribution about the Pc macrocycle and the intracellular localization of the cationic ZnPcs mainly determine their photodynamic activity.

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Section: Introductionmentioning

confidence: 99%

Syntheses and Photodynamic Activity of Pegylated Cationic Zn(II)-Phthalocyanines in HEp2 Cells

Ongarora¹,

Hu²,

Verberne-Sutton³

et al. 2012

Theranostics

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“…Recently, therapeutic potential of liposome-encapsulated anticancer drug has been demonstrated in cancer chemotherapy: polyethyleneglycol-modified liposomes encapsulating benzoporphyrin are useful for passive targeting to tumor tissues, 7 and Ala-Pro-Arg-Glypolyethyleneglycol-modified liposomes encapsulating adriamycin have affinity for human umbilical vein endotherial cells. 8 Jin et al reported that a poly(D,Llactide-co-glycolide) (PLGA) nanoparticle containing SR-2508 (etanidazole), a hypoxic radiosensitizer, was more significant than free drug in human tumor cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…5 On the other hand, in cancer chemotherapy, encapsulation of cancer drugs in liposome has been developed to be useful as the drug carrier and for prevention from severe side effects of cancer drugs. [6][7][8] We hypothesized that when Pmz was encapsulated in liposome, the radiosensitizing effect on hypoxic cancer * Author to whom correspondence should be addressed. cells was enhanced due to intracellular uptake was promoted through endocytosis including phagocytosis for lager particles such as liposomes.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Radiosensitization by Liposome-Encapsulated Pimonidazole for Anticancer Effects on Human Melanoma Cells

Kato

Kimura²,

Kageyama³

et al. 2012

j. nanosci. nanotech.

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The nitroimidazole-related hypoxic radiosensitizer, pimonidazole (Pmz) was encapsulated in liposome composed of dipalmitoylphosphatidylcholine, cholesterol and dipalmitoylphosphatidylglycerol (molar ratio = 1:1:0.2; diameter = 112.9 nm), and the radiosensitization was evaluated in human melanoma cells HMV-II. Cell proliferation was examined by WST-8 assay after X-ray irradiation in the presence of liposomal Pmz or free-Pmz under hypoxic conditions. On 7th day after X-ray irradiation of 5 Gy, cell proliferation decreased more markedly in the administration of liposomal Pmz than free-Pmz at equivalent Pmz doses. Chromatin fragmentation or nuclear condensation was observed in liposomal Pmz-treated HMV-II cells. Radiosensitization was enhanced dose-dependently along with Pmz amounts of 250-2000 microM contained in liposomal Pmz. Intracellular uptake was more abundant for liposomal Pmz for 60-240 min than for free-Pmz. Thus liposomal Pmz has a potential to overcome radiation resistance in hypoxia, owing to enhanced intracellular uptake by melanoma cells.

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“…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: 88%

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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PEGylation of Liposome Decreases the Susceptibility of Liposomal Drug in Cancer Photodynamic Therapy

Cited by 37 publications

References 6 publications

Syntheses and Photodynamic Activity of Pegylated Cationic Zn(II)-Phthalocyanines in HEp2 Cells

Syntheses and Photodynamic Activity of Pegylated Cationic Zn(II)-Phthalocyanines in HEp2 Cells

Enhanced Radiosensitization by Liposome-Encapsulated Pimonidazole for Anticancer Effects on Human Melanoma Cells

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

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