Possibility of active targeting to tumor tissues with liposomes

Maruyama, Kazuo; Ishida, Osamu; Takizawa, Tomoko; Moribe, Kunikazu

doi:10.1016/s0169-409x(99)00042-3

Cited by 187 publications

(97 citation statements)

References 28 publications

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“…This small size is important as it strongly increases the possibility of passive extravasation of TsPLP. 23 In fact, the complex appear to be more compact than the original TsLP, which has a size of 329743 nm. 28 However, inclusion of PEG into the complex did result in a significant decrease in the zeta potential, which is a measure of the overall charge of the molecule.…”

Section: Physical Characteristics Of Tsplpmentioning

confidence: 97%

A sterically stabilized immunolipoplex for systemic administration of a therapeutic gene

Pirollo

Rait

et al. 2004

Gene Ther

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A sterically stabilized immunolipoplex (TsPLP), containing an antitransferrin receptor single-chain antibody fragment (TfRscFv)-PEG molecule, has been developed to specifically and efficiently deliver a therapeutic gene to tumor cells. A postcoating preparation strategy was employed in which a DNA/lipid complex (lipoplex) was formed first and then sequentially conjugated with PEG and TfRscFv. The complex prepared by this method was shown to be superior in ability to deliver genes to tumor cells than when prepared by a common precoating strategy, in which DNA is mixed with TfRscFv-PEG conjugated liposome. Using prostate cancer cell line DU145, a comparison was made between the in vitro and in vivo gene delivery efficiencies of four complexes, Lipoplex (LP), PEG-Lipoplex (PLP), TfRscFv-PEG-Lipoplex (TsPLP) and our standard TfRscFv-Lipoplex (TsLP). In vitro, the order of transfection efficiency was TsLP4LPETsPLP4PLP. However, in vivo the order of transfection efficiency, after systemic administration via the tail vein, was TsPLP4TsLP4LP or PLP with TsPLPmediated exogenous gene expression in tumor being twofold higher than when mediated by TsLP. This suggests that the in vitro transfection efficiency of TsPLP was not indicative of its in vivo efficiency. In addition, it was found that the level of exogenous gene expression in the tumor mediated by TsPLP was higher than that mediated by TsLP and did not decrease over the time. More importantly, high exogenous gene expression in tumor, but low expression in liver, was observed after an i.v. delivery of TsPLP carrying either the GFP reporter gene or the p53 gene, indicating that tumor preferential targeting was maintained by this complex in the presence of PEG. These findings show that incorporation of PEG into our targeted lipoplex results in a more efficient delivery of the complex to the tumor cells, possibly by inhibiting the first pass clearance observed with non-PEG containing liposomes. Therefore, these data demonstrate that TsPLP is a improvement over our previously established tumor targeted gene delivery complex for systemic gene therapy of cancer.

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Section: Physical Characteristics Of Tsplpmentioning

confidence: 97%

A sterically stabilized immunolipoplex for systemic administration of a therapeutic gene

Pirollo

Rait

et al. 2004

Gene Ther

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“…It was reported that the addition of 5 mol % of PEG to the surface of liposomes could drastically inhibit the binding and uptake of liposomes [35]. To enhance the specific cellular uptake while at the same time decreasing the non-specific phagocytosis by immune cells, PEGylation in combination with active targeting could be an option [36,37]. Quantitative analysis by flow cytometry (Fig.…”

Section: Folate Receptor Expressionmentioning

confidence: 99%

Microfluidic synthesis of multifunctional liposomes for tumour targeting

Ran

Middelberg

Zhao

2016

Colloids and Surfaces B: Biointerfaces

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Graphical abstract Highlights Targeted liposomes can be prepared in the one-step microfluidic device  Size and surface properties can be controlled easily  This microfluidic method directed targeted liposomes possess selective cell uptake enhancement in both 2D and 3D model.  At the same time, these liposomes can reduce phagocytosis. AbstractNanotechnology has started a new era in engineering multifunctional nanoparticles for diagnosis and therapeutics by incorporating therapeutic drugs, targeting ligands, stimuliresponsive release and imaging molecules. However, more functionality requires more complex synthesis processes, resulting in poor reproducibility, low yield and high production cost, hence difficulties in clinical translation. Herein we report a one-step microfluidic method for making multifunctional liposomes. Three formulations were prepared using this simple method, including plain liposomes, PEGylated liposomes and folic acid functionalised liposomes, all with a fluorescence dye encapsulated for imaging. The size and surface properties of these liposomes can be precisely controlled by simply tuning the flow rate ratio and the ratio of the lipids to PEGylated lipid (DSPE-PEG2000) and to the DSPE-PEG2000-Folate, respectively. The synthesised liposomes remained stable under mimic serum conditions.Compared to the plain liposomes and PEGylated liposomes, the targeted folic acid functionalised liposomes exhibited enhanced cellular uptake by the FA receptor positive SKOV3 cells, but not the negative MCF7 cells, and this enhanced uptake could be inhibited by adding excess free folic acid, indicating high specificity of FA ligand-receptor endocytosis.Further evaluation using the 3D tumour spheroid model also showed higher internalisation of the targeted liposome formulation in comparison with the PEGylated one. To the best of our knowledge, this work demonstrates for the first time the versatility of this microfluidic method for making different liposome formulations in a single step, their superior physicochemical properties as well as the enhanced cellular uptake and tumour spheroid uptake of the targeted liposomes.

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“…In contrast, a liposome surface can be modified with a suitable antibody or ligand for intracellular targeting. 32 Maruyama et al 33 reported that pendant-type PEG immunoliposomes consist of couplings of the FabЈ fragments of MAb specific for human CEA. They showed that these modified liposomes evaded RES uptake and remained in the circulation for a long time, resulting in enhanced accumulation of liposomes in solid tumor, which expresses CEA.…”

Section: Discussionmentioning

confidence: 99%

Intracellular targeting therapy of cisplatin‐encapsulated transferrin‐polyethylene glycol liposome on peritoneal dissemination of gastric cancer

Iinuma¹,

Maruyama²,

Okinaga³

et al. 2002

Intl Journal of Cancer

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199

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Peritoneal dissemination in gastric cancer is a common fatal clinical condition with few effective therapies available. We studied the therapeutic effect of a tumor-targeting drug delivery system that uses cisplatin-encapsulated and Tf-conjugated PEG liposomes (Tf-PEG liposomes) in nude mice with peritoneal dissemination of human gastric cancer cells. Small unilamellar Tf-PEG, PEG or DSPC/CH liposomes (bare liposomes) encapsulating cisplatin were prepared by reversephase evaporation followed by extrusion. Electron microscopic studies revealed that Tf-PEG liposomes were internal- Key words: liposome; targeting; transferrin; peritoneal dissemination; gastric cancerPeritoneal dissemination is the most frequent noncurative factor and the most common type of recurrence after curative surgery in patients with gastric cancer. 1 Control of this metastasis is one of the most important challenges in treating gastric cancer. There have been few reports of effective treatment for peritoneal dissemination in patients with gastric cancer. 2,3 As a clinical locoregional chemotherapy, various anticancer drugs in solution form have been administered i.p. to expose the drug directly to peritoneal tumor cells. 4 However, small water-soluble molecules, such as cisplatin or mitomycin C, are absorbed easily through the large peritoneal surface into the circulating blood. It is difficult to maintain a high drug concentration for a long time in the peritoneal cavity. 5,6 Therefore, i.p. administration of anticancer drugs in solution form does not always produce the desired effect.Liposomes, known to be drug carriers, have various advantages. 7,8 First, they encapsulate various drugs such as water-soluble, lipid-soluble or high m.w. substances and release them in a sustained manner. Second, the antigenicity and toxicity of liposomes are very low because they consist of lipid, which is a natural component of organisms. Third, the biodistribution of liposomes can be controlled by the size or lipid component. Fourth, various materials, such as antibodies or chemical compounds, can modify the surfaces of liposomes. However, the therapeutic application of liposomes has been limited by their rapid clearance from the bloodstream and by their uptake by the RES. Recent efforts have been made to reformulate the liposome composition, to reduce its affinity to the RES. Liposomes modified with amphipathic PEG are not readily taken up by macrophages in the RES and, hence, stay in the circulation for a relatively long time. 9 -14 To increase the therapeutic effect and decrease side effects, tumor-specific targeting therapy has been advocated. Intracellular targeting using iron-saturated Tf as a ligand for receptor-mediated endocytosis has attracted attention. Tf is a glycoprotein that transports ferric ions in the body and the Tf receptor is internalized into cells by endocytosis through the binding of Tf. This receptormediated endocytosis is a normal physiologic process by which iron is delivered to cells. [15][16][17] Also, the Tf receptor concen...

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Possibility of active targeting to tumor tissues with liposomes

Cited by 187 publications

References 28 publications

A sterically stabilized immunolipoplex for systemic administration of a therapeutic gene

A sterically stabilized immunolipoplex for systemic administration of a therapeutic gene

Microfluidic synthesis of multifunctional liposomes for tumour targeting

Intracellular targeting therapy of cisplatin‐encapsulated transferrin‐polyethylene glycol liposome on peritoneal dissemination of gastric cancer

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