Targeted Delivery Systems of Small Interfering RNA by Systemic Administration

Kawakami, Shigeru; Hashida, Mitsuru

doi:10.2133/dmpk.22.142

Cited by 95 publications

(76 citation statements)

References 77 publications

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“…4 The other obstacles to the delivery of siRNAs in vivo, such as degradation by nuclease(s) in blood and interaction with blood components, indeed exist. 5 To overcome these obstacles, many delivery systems, such as hydrodynamic approaches 6 and bioconjugating approaches including cationic liposomes, 7 cationic polymers, 8 and cell penetrating peptides, 9 have been developed. However, thus far there is little conclusive method.…”

mentioning

confidence: 99%

Systemic delivery of siRNA specific to tumor mediated by atelocollagen: Combined therapy using siRNA targeting Bcl‐xL and cisplatin against prostate cancer

Nagahara

Makita

et al. 2009

Intl Journal of Cancer

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The largest obstacle to the effective use of short interfering RNA (siRNA) in an animal body is the ability to deliver it to the target tissue. Here we showed a systemic delivery method of siRNA specific to pregrown solid tumors via atelocollagen. Atelocollagen facilitated the selective uptake of siRNA into the tumors when an siRNA/atelocollagen complex was administered intravenously to mice. We chose a Bcl‐xL protein as a model target to prove the therapeutic efficacy of the atelocollagen‐mediated method. Bcl‐xL acts as an anti‐apoptotic factor, which is overexpressed in many cancers, including prostate cancer. One of the four designed siRNAs to human Bcl‐xL potently inhibited the expression of Bcl‐xL by the PC‐3 human prostate cancer cell line in vitro, leading to cell apoptosis. Intravenous injections for3 consecutive days (siRNA, 100 μg/injection per day as a complex with atelocollagen) effectively downregulated Bcl‐xL expression in the PC‐3 xenograft. We administered four series of 3 consecutive days of intravenous injections each, for a total of 12 injections, which significantly inhibited tumor growth when the treatment was combined with cisplatin (2 mg/kg). Local injection of Bcl‐xL siRNA also potently inhibited tumor growth. All of the tumors treated with Bcl‐xL siRNA/atelocollagen complex via both intravenous and intratumoral injection showed terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling‐positive apoptosis. There were no severe side effects such as interferon‐α induction and liver or renal damage in mice. Our results indicate that systemic delivery of siRNA via atelocollagen, which specifically targets tumors, is safe and feasible for cancer therapy. © 2009 UICC

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mentioning

confidence: 99%

Systemic delivery of siRNA specific to tumor mediated by atelocollagen: Combined therapy using siRNA targeting Bcl‐xL and cisplatin against prostate cancer

Nagahara

Makita

et al. 2009

Intl Journal of Cancer

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“…RNA interference (RNAi) can be induced by double-stranded siRNA, consisting of 21-25 nucleotides, which is incorporated into the RNAi-induced silencing complex and is a guide for cleavage of complementary target messenger RNA (mRNA) in the cytoplasm [169,170]. An effective delivery system is essential for the application of siRNA as clinical treatment.…”

Section: Nucleic Acid Deliverymentioning

confidence: 99%

Glycosylation-mediated targeting of carriers

Kawakami

Hashida

2014

Journal of Controlled Release

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For safe and effective therapy, drugs should be delivered selectively to their target tissues or cells at an optimal rate. Drug delivery system technology maximizes the therapeutic efficacy and minimizes unfavorable drug actions by controlling their distribution profiles. Ligand-receptor binding is a typical example of specific recognition mechanisms in the body; therefore, ligand-modified drug carriers have been developed for active targeting based on receptor-mediated endocytosis. Among the various ligands reported thus far, sugar recognition is a promising approach for active targeting because of their high affinity and expression. Glycosylation has been applied for both macromolecular and liposomal carriers for cell-selective drug targeting.Recently, the combination of ultrasound exposure and glycosylated bubble liposomes has been developed. In this review, recent advances of glycosylation-mediated targeted drug delivery systems are discussed.

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“…4 and Hela cells using the MTT assay. As shown in Figure 5, the Man-PEI25k/DNA complexes exhibited much lower levels of cytotoxicity towards the DC2.4 and HeLa cells than the unmodified PEI25k/DNA complexes at all of the concentrations tested.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

“…The use of PEI as a gene carrier, however, has been limited because of its high cytotoxicity and non-specific interactions in vivo [3]. Various modifications have been applied to PEI to improve its biocompatibility, reduce its toxicity and increase its target specificity [4]. One efficient strategy for overcoming these limitations could be to add targeting ligands to polyplexes that would enhance cell-specific gene delivery through receptor-mediated cellular uptake [5,6].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Mannosylated Polyethylenimine and Its Potential Application as Cell-Targeting Non-Viral Vector for Gene Therapy

et al. 2014

Polymers

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Mannose polyethylenimine with a molecular weight of 25 k (Man-PEI25k) was synthesized via a phenylisothiocyanate bridge using mannopyranosylphenyl isothiocyanate as a coupling reagent, and characterized by 1 H NMR (nuclear magnetic resonance) and FT-IR (Fourier transform infrared spectroscopy) analysis. Spherical nanoparticles were formed with diameters of 80-250 nm when the copolymer was mixed with DNA at various charge ratios of copolymer/DNA (N/P). Gel electrophoresis demonstrated that the DNA had been condensed and retained by the PEI derivates at low N/P ratios. The Man-PEI25k/DNA complexes were less cytotoxic than the PEI complexes with a molecular weight of 25 k (PEI25k) at the same N/P ratio. Laser scan confocal microscopy and flow cytometry confirmed that the Man-PEI25k/DNA complexes gave higher cell uptake efficiency in (Dendritic cells) DC2.4 cells than HeLa cells. The transfection efficiency of Man-PEI25k was higher than that of PEI25k towards DC2.4 cells. These results indicated that Man-PEI25k OPEN ACCESSPolymers 2014, 6 2574 could be used as a potential DC-targeting non-viral vector for gene therapy.

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Targeted Delivery Systems of Small Interfering RNA by Systemic Administration

Cited by 95 publications

References 77 publications

Systemic delivery of siRNA specific to tumor mediated by atelocollagen: Combined therapy using siRNA targeting Bcl‐xL and cisplatin against prostate cancer

Systemic delivery of siRNA specific to tumor mediated by atelocollagen: Combined therapy using siRNA targeting Bcl‐xL and cisplatin against prostate cancer

Glycosylation-mediated targeting of carriers

Synthesis of Mannosylated Polyethylenimine and Its Potential Application as Cell-Targeting Non-Viral Vector for Gene Therapy

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