Polymer brush-stabilized polyplex for a siRNA carrier with long circulatory half-life

Sato, Ayumi; Choi, Sung Won; Hirai, Masamichi; Yamayoshi, Asako; Moriyama, Rui; Yamano, Takeshi; Takagi, Motoki; Kano, Arihiro; Shimamoto, Akira; Maruyama, Atsushi

doi:10.1016/j.jconrel.2007.04.018

Cited by 95 publications

(69 citation statements)

References 39 publications

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“…PEG in high concentration has been widely used as a successful strategy to incorporate hydrophilic chains or to change the surface charges of the therapeutic nanoparticles, resulting in increased blood circulation time and decreased phagocytosis possibly due to decreased nonspecific interaction of the complex with serum components (14). In this study, PEG was used at a low concentration to control the pore structure and enhance the release of the cargo.…”

Section: Discussionmentioning

confidence: 99%

Silica-Antibiotic Hybrid Nanoparticles for Targeting Intracellular Pathogens

Seleem

Munusamy²,

Ranjan

et al. 2009

Antimicrob Agents Chemother

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We investigated the capability of biodegradable silica xerogel as a novel carrier of antibiotic and the efficacy of treatment compared to that with the same dose of free drug against murine salmonellosis. The drug molecules (31%) entrapped in the sol-gel matrix remained in biologically active form, and the bactericidal effect was retained upon drug release. The in vitro drug release profiles of the gentamicin from the xerogel and that from the xerogel-polyethylene glycol (PEG) were distinctly different at pH 7.4. A delayed release of gentamicin was observed from the silica xerogel network (57% in 33 h), and with the addition of 2% PEG, the release rate reached 90% in 33 h. Administration of two doses of the silica xerogel significantly reduced the Salmonella enterica serovar Typhimurium load in the spleens and livers of infected AJ 646 mice. The silica xerogel and xerogel-PEG achieved a 0.45-log and a 0.41-log reduction in the spleens, respectively, while for the free drug there was no reduction. On the other hand, silica xerogel and xerogel-PEG achieved statistically significant 1.13-log and 1.15-log reductions in the livers, respectively, while for the free drug the reduction was a nonsignificant value of 0.07 log. This new approach, which utilizes a room-temperature synthetic route for incorporating therapeutic drugs into the silica matrix, should improve the capability for targeting intracellular pathogens.

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Section: Discussionmentioning

confidence: 99%

Silica-Antibiotic Hybrid Nanoparticles for Targeting Intracellular Pathogens

Seleem

Munusamy²,

Ranjan

et al. 2009

Antimicrob Agents Chemother

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“…Poly(ethylene glycol) (PEG) has uncharged hydrophilic characteristic, and high steric stabilization with non-toxic resulting in dramatically changing the charge of biomaterials, which thus has been a major strategy to decrease the nonspecific interactions of complexes with serum components, and thereby increase blood circulation time. (Sato et al 2007;Torchilin 2007) In our previous study (Zhao et al 2007), PEG chains were introduced into hydrophobic poly(ε-caprolactone) (PCL) NPs to improve the hydrophilicity of NPs and prolong the longevity of polymeric NPs in blood stream. Results showed that, after intravenous (i.v.)…”

Section: Instructionmentioning

confidence: 99%

Influence of PEG chain on the complement activation suppression and longevity in vivo prolongation of the PCL biomedical nanoparticles

Shan

Yuan

Liu

et al. 2009

Biomed Microdevices

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The process of opsonization is the major biological barrier to the injectable polymeric nanoparticles (NPs). Complement protein is one kind of opsonins and it can be activated potentially by the negative charged particles. The fragment C3b generated by complement activation could subsequently induce the opsonization on the NPs surface. The aim of our work was to examine the relationship between the hydrophilic poly(ethylene glycol) (PEG) chain on the surface of NPs and particles longevity in vivo from the biological point of view such as complement activation (C3 cleavage) as well as uptake by macrophages. The studies showed that the introduction of PEG chains led to slightly smaller NPs with lower polydispersities than those prepared from naked poly(epsilon-caprolactone) (PCL) and enhanced the zeta potential of NPs from -27.17 mV to -6.046 mV. It was also found that PEG hydrophilic chain could decrease the C3 cleavage and remarkably suppress opsonization and phagocytosis subsequently. In biodistribution investigations in vivo, as a control, PCL NPs were present in MPS tissues in the first 5 min followed by metabolism elimination rapidly, whereas the PEGylated NPs had more particles blood retention in vivo after injection. In fact, in present work, it has been convinced that these results in vivo could be predicted by the in vitro fluorescent phagocytosis model and the extent of complement activation in advance.

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“…(e) Retention of the RecQL1-siRNA/PEI complex in the circulation blood of mice. RecQL1-siRNA fluorescently labeled with tetramethylrhodamine (TAMRA) at the 5′-terminus of the sense strand was mixed with PEI, and the retention time in the circulating blood was investigated according to the method described by Sato et al (31) The labeled RecQL1-siRNA/PEI complex was injected into the tail vein and was extracted from the eye vein at 1, 5, and 10 min after the injection. Parts of the extracted blood samples were extracted with phenol-chloroform and were analyzed by using 10% polyacrylamide gel electrophoresis.…”

Section: Resultsmentioning

confidence: 99%

Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models

et al. 2008

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Small interfering RNAs (siRNAs) are expected to have a medical application in human therapy as drugs with a high specificity for their molecular target mRNAs. RecQL1 DNA helicase in the human RecQ helicase family participates in DNA repair and recombination pathways in the cell cycle of replication. Silencing the RecQL1 expression by RecQL1-siRNA induces mitotic death in vitro specifically in growing cancer cells. By contrast, the same RecQL1 silencing does not affect the growth of normal cells, emphasizing that RecQL1 helicase is an ideal molecular target for cancer therapy. In this study, we show that local and systemic administration of RecQL1-siRNA mixed with polyethyleneimine polymer or cationic liposomes prevented cancer cell proliferation in vivo in mouse models of cancer without noticeable adverse effects. The results indicate that RecQL1-siRNA in a complex with a cationic polymer is a very promising anticancer drug candidate, and that in particular, RecQL1-siRNA formulated with a cationic liposome has an enormous potential to be used by intravenous injection for therapy specific for liver cancers, including metastasized cancers from the colon and pancreas. (Cancer Sci 2008; 99: 1227-1236) H uman RecQL1 DNA helicase (RecQL1), a member of the RecQ helicase family, participates in the maintenance of genomic integrity and is highly up-regulated in rapidly growing cells, including various cancers and transformed cells.(1-5)RecQL1 unwinds specific DNA in vitro ATP-dependently and can increase base matching ATP-independently. (6,7) It is assumed to participate in the mismatch repair pathway in vivo because it binds to the incision activity of human EXO1 and the mismatch repair recognition complex MSH2/6.(8) Also, RecQL1 acts as an enzyme that resolves Holliday junctions during cell proliferation. (9) Consequently, down-regulation of RecQL1 expression in HeLa cells by RNA interference (RNAi) increases sister chromatid exchanges resulting from unprocessed Holliday junction structures, (10) . Although RecQL1-deficient mice show no apparent phenotypic differences when compared with wild-type mice, embryonic fibroblasts from RecQL1-deficient mice are sensitive to ionizing radiation (11) (and our unpublished data Sakamoto et al. 1999). All these findings collectively showed that RecQL1 suppresses chromosomal instability by participating in DNA repair associated with cell proliferation, but its function seems to be nonessential and complemented by other cellular repair system(s).Silencing RecQL1 in cancer cells by RNAi with siRNA induces mitotic catastrophe and death in a wide range of cancer cells that have defects in the cell cycle checkpoint system.(12) By contrast, the same silencing does not cause mitotic death in growing normal cells that have a competent checkpoint system, even though their cell cycles slowed down. To test the efficacy of RecQL1-siRNA in vivo, we previously studied the multicellular cancer spheroids system, a three dimensional (3-D) model that uses human hepatocarcinoma HuH-7 cell lines to m...

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Polymer brush-stabilized polyplex for a siRNA carrier with long circulatory half-life

Cited by 95 publications

References 39 publications

Silica-Antibiotic Hybrid Nanoparticles for Targeting Intracellular Pathogens

Silica-Antibiotic Hybrid Nanoparticles for Targeting Intracellular Pathogens

Influence of PEG chain on the complement activation suppression and longevity in vivo prolongation of the PCL biomedical nanoparticles

Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models

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