A new peptide motif present in the protective antigen of anthrax toxin exerts its efficiency on the cellular uptake of liposomes and applications for a dual-ligand system

Kibria, Golam; Hatakeyama, Hiroto; Harashima, Hideyoshi

doi:10.1016/j.ijpharm.2011.03.010

Cited by 16 publications

(9 citation statements)

References 40 publications

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“…Nanoparticles modified with the R8 peptide have been successful in delivering several substances, such as low molecular drugs, proteins and nucleic acids, under in vitro and in vivo conditions [11]. The high cellular affinity of R8 peptide can be used for most type of cells: fibroblast cells [14], hepatic cells [20], endothelial cells [21], tumor cells [22], immune cells [23,24] and so on. In this study, CWS-NP/LEEL was efficiently internalized into MBT-2 cells (Figure 3A-3C).…”

Section: Discussionmentioning

confidence: 99%

Nanoparticulation of BCG-CWS for application to bladder cancer therapy

Nakamura

Fukiage

Higuchi

et al. 2014

Journal of Controlled Release

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The Mycobacterium bovis Bacille Calmett-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166 nm-sized lipid particles. The BCG-CWS encapsulated nano particle (CWS-NP) has a high uniformity and can be easily dispersed. Thus, it has the potential for use as a packaging method that would advance the scope of applications of BCG-CWS as a bladder cancer drug. In a functional evaluation, CWS-NP was efficiently taken up by mouse bladder tumor cells (MBT-2) in vitro and inhibited tumor growth in mice bearing MBT-2 tumors. Moreover, intravesically administered CWS-NP showed significant antitumor effects in a rat model with in naturally developed bladder cancer. An enhancement in Th1 differentiation by CWS-NP was also confirmed in human T cells. In conclusion, CWS-NP represents a promising delivery system for BCG-CWS for clinical development as a potent bladder cancer drug.

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Section: Discussionmentioning

confidence: 99%

Nanoparticulation of BCG-CWS for application to bladder cancer therapy

Nakamura

Fukiage

Higuchi

et al. 2014

Journal of Controlled Release

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“…The combination of a cell-penetrating peptide with a targeting peptide conjugate has recently been reported as a potential strategy to achieve cell-type selective uptake of TAT modified liposomes [10][11][12] .…”

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confidence: 99%

Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment

et al. 2014

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Specific targeting and cellular internalization are key properties for carriers of antitumor therapeutic agents. Here, we develop a drug carrier through the attachment of substrate of endoprotease legumain, alanine-alanine-asparagine (AAN), to cell-penetrating peptides (TAT, trans-activating factor). The addition of the AAN moiety to the fourth lysine in the TAT creates a branched peptide moiety, which leads to a decrease in the transmembrane transport capacity of TAT by 72.65%. Legumain efficiently catalyses the release of TAT-liposome from the AAN-TAT-liposome and thereby recovers the penetrating capacity of TAT. Doxorubicin carried by the AAN-TAT-liposome led to an increase in the tumoricidal effect of doxorubicin and a reduction in its systemic adverse effects in comparison with doxorubicin carried by a control delivery system. Thus, the specific targeting and high efficiency of this delivery platform offers a novel approach to limit the toxicity of anticancer agents as well as increasing their efficacy in cancer therapy.

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“…TMSP or r 9 peptides were conjugated with DSPE-PEG 2000 -MAL (1.2:1 molar ratio) in DMF contained triethylamine (TEA, 5 eq) at room temperature (20e 25 C) for 24 h under vigorous stirring [23]. The reaction mixture was dialyzed (molecular weight cutoff (MWCO) 3.5 kDa) in distilled water for 48 h to remove the DMF and unreacted peptides.…”

Section: Synthesis Of Dspe-peg 2000 -Tmsp and Dspe-peg 2000 -Rmentioning

confidence: 99%