RGD-based active targeting of novel polycation liposomes bearing siRNA for cancer treatment

Yonenaga, Norihito; Kenjo, Eriya; Asai, Tomohiro; Tsuruta, Atsushi; Shimizu, Kosuke; Dewa, Takehisa; Nango, Mamoru; Oku, Naoto

doi:10.1016/j.jconrel.2011.10.004

Cited by 78 publications

(57 citation statements)

References 23 publications

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“…[83][84][85][86][87] Another peptide ligand, the asparagine-glycine-arginine (NGR) motif peptide, is identified as a ligand for CD13 or aminopeptidase N overexpressed on tumor endothelial cells and tumor cells. 88) NGR motif peptides have been successfully used to deliver drugs as well as liposomes to tumor vasculature.…”

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

425

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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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

425

276

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“…Discussion RGD (Arg-Gly-Asp) is a tripeptide sequence that has been used as a vehicle for various chemotherapeutic agents, nanoparticles, and gene therapy targets 17,[20][21][22] due to its high affinity with integrin a v b 3 . Integrin a v b 3 plays a crucial role in angiogenesis and in facilitating tumor cell metastasis and invasion and has been studied intensively as a molecular target for both tumor image tracers and tumor therapy.…”

Section: Correlation Ofmentioning

confidence: 99%

^99mTc-3P-RGD₂ Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin α_vβ₃-Targeted Therapy

Qiu

et al. 2014

Cancer Biotherapy and Radiopharmaceuticals

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Purpose: This study was to demonstrate the utility of 99m Tc-3P-RGD 2 micro-single-photon emission computed tomography/computed tomography (SPECT/CT) for the integrin a v b 3 expression quantification in NCI-H446 and A549 lung cancer xenografts. Materials and Methods: 99m Tc-3P-RGD 2 was prepared with high radiochemical purity (97% -2%) and showing high in vitro stability. The in vitro affinities of 99m Tc-3P-RGD 2 to NCI-H446 and A549 tumor cells were analyzed with c-counter, while the in vivo uptakes in NCI-H446 and A549 xenografts were evaluated with micro-SPECT/CT. The region of interest was drawn over the tumor site and contralateral muscle on the SPECT/ CT image, and the tumor to nontumor (T/NT) ratio was calculated to estimate a v b 3 expression and tumor uptake. The expressions of integrin a v b 3 in vitro and in vivo were analyzed using a flow cytometer and immunofluorescence. Results: Micro-SPECT/CT demonstrated focal uptake in the tumors. T/NT ratio in NCI-H446 xenografts was significantly higher compared with the A549 tumor model, as 5.92 -0.82 and 3.62 -0.91, respectively, with p < 0.05. In addition, integrin a v b 3 expression in NCI-H446 cells was significantly higher compared with the A549 cells, which was consistent with the imaging data. A linear relationship was observed between 99m Tc-3P-RGD 2 uptake and a v b 3 expression (R 2 = 0.7667, p < 0.001). Conclusion:99m Tc-3P-RGD 2 SPECT/CT could be used to quantify integrin a v b 3 expression within tumors, providing a rational basis for integrin a v b 3 -targeted cancer therapy.

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“…9) In brief, DCP-TEPA, DOPE, DPPC, and cholesterol (0.25 : 1 : 0.75 : 1) were dissolved in t-butyl alcohol for freezedrying, and hydrated in RNase-free water. The prepared TEPA-PCL were extruded 10 times through a polycarbonate membrane filter with 100-nm pores (Nuclepore, Maidstone, U.K.) by using an extruder (Lipex, Vancouver, Canada).…”

Section: )mentioning

confidence: 99%

“…9) Here, we investigated the antiproliferative effect of the therapeutic siCocktail-C targeting c-myc, MDM2, and VEGF carried by this formulation. As shown in Fig.…”

Section: Antiproliferative Effect Of Sirna-c Formulated In Rgd-peg-pcmentioning

confidence: 99%

“…10,11) By use of mice bearing B16F10-luc2 murine melanoma stably expressing the luciferase 2 gene (Luc2), we observed the knockdown of luciferase expression in vivo after systemic injection of cholesterol-conjugated siRNA for Luc2 (siLuc2-C) carried by RGD-PEG-PCL. 9) In the present study, we used these RGD-PEG-PCL for delivering therapeutic siRNA for cancer treatment. Song et al previously reported that siRNAs for c-myc, MDM2, and vascular endothelial growth factor (VEGF) suppressed B16 tumor growth 12) ; and Li et al also observed inhibition of B16F10 metastasis with this siRNA cocktail.…”

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confidence: 99%

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Systemic Delivery of Small Interfering RNA by Use of Targeted Polycation Liposomes for Cancer Therapy

Kenjo

Asai

Yonenaga

et al. 2013

Biological & Pharmaceutical Bulletin

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Novel polycation liposomes decorated with cyclic(Cys-Arg-Gly-Asp-d-Phe) peptide (cyclicRGD)-polyethylene glycol (PEG) (RGD-PEG-polycation liposomes (PCL)) were previously developed for cancer therapy based on RNA interference. Here, we demonstrate the in vivo delivery of small interfering RNA (siRNA) to tumors by use of RGD-PEG-PCL in B16F10 melanoma-bearing mice. Pharmacokinetic data obtained by positron emission tomography showed that cholesterol-conjugated siRNA formulated in RGD-PEG-PCL markedly accumulated in the tumors. Delivered by RGD-PEG-PCL, a therapeutic cocktail of siRNAs composed of cholesterol-conjugated siRNAs for c-myc, MDM2, and vascular endothelial growth factor (VEGF) were able to significantly inhibit the growth of B16F10 melanoma both in vitro and in vivo. These data suggest that targeted delivery of siRNAs by use of RGD-PEG-PCL has considerable potential for cancer treatment.

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RGD-based active targeting of novel polycation liposomes bearing siRNA for cancer treatment

Cited by 78 publications

References 23 publications

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

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

^99mTc-3P-RGD₂ Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin α_vβ₃-Targeted Therapy

Systemic Delivery of Small Interfering RNA by Use of Targeted Polycation Liposomes for Cancer Therapy

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RGD-based active targeting of novel polycation liposomes bearing siRNA for cancer treatment

Cited by 78 publications

References 23 publications

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

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

99mTc-3P-RGD2 Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin αvβ3-Targeted Therapy

Systemic Delivery of Small Interfering RNA by Use of Targeted Polycation Liposomes for Cancer Therapy

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^99mTc-3P-RGD₂ Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin α_vβ₃-Targeted Therapy