Photochemically enhanced cellular delivery of cell penetrating peptide‐PNA conjugates

Shiraishi, Toshihiko; Nielsen, Peter E.

doi:10.1016/j.febslet.2006.01.077

Cited by 81 publications

(65 citation statements)

References 16 publications

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“…However, PNA-CPP conjugates were released from the endosomal trap by addition of chloroquine (76). Splice correction by PNA-CPP and PMO-CPP conjugates using luciferase reporter gene has been achieved (77)(78)(79)(80)(81). In vitro CPP-mediated delivery of splice correcting ON analogs has been demonstrated for nuclear targeting (82).…”

Section: Delivery Of Nucleic Acids By Cpp-mediated Cargo Deliverymentioning

confidence: 99%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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SummaryNovel classes and applications of cell-penetrating peptides (CPPs) are being constantly discovered since they were first identified 2 decades ago. These short cationic peptides (nanomolecules) either by covalent binding or by noncovalent binding can traverse cell membranes and deliver a variety of molecules that are unable to overcome the permeability barrier in their own capacity. The ability of the CPPs to deliver variety of macromolecules, such as oligonucleotides, therapeutic drugs, proteins, and medical imaging agents, by forming nanoparticulate carriers in a range of cells has led them to emerge as a potential tool for both macromolecule delivery application and to gain insight into the fundamentals of mechanism of cellular uptake across the plasma membrane. This review explores the recent advances, challenges, and future prospects in the field of CPP-mediated cargo delivery in mammalian and plant cells. Studies have been conducted into the peptide chemistry and stability of CPP-macromolecular complexes. Most of the CPPs have been shown to be nontoxic and do not interfere with the functionality of the macromolecules delivered across the cell membrane. The mechanism of uptake of CPP-cargo complexes and the uptake of CPPs alone across the plasma membrane remains unresolved. As the world of CPPs is rapidly advancing in both mammalian and plant system, there is a promising future for the various applications of transduction and transfection into intact cells.

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Section: Delivery Of Nucleic Acids By Cpp-mediated Cargo Deliverymentioning

confidence: 99%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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“…First, the entry mechanism implies the use of pathways that are sensitive to lysosomotrophic agents, such as chloroquine and sucrose [57,58]. Moreover, the efficacy of the cell uptake is improved by coincubation of Tat with another peptide derived from the hemagglutinin protein which has membrane fusogenic properties [59], or by the use of photochemical internalization mediated by a membrane soluble photosensitizer [60].…”

Section: Cpps and Cell Entrymentioning

confidence: 99%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

315

272

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During the last decade, the potential of peptides for drug delivery into cells has been highlighted by the discovery of several cell-penetrating peptides (CPPs). CPPs are very efficient in delivering various molecules into cells. However, except in some specific cases, their lack of cell specificity remains the major drawback for their clinical development. At the same time, various peptides with specific binding activity for a given cell line (cell-targeting peptides) have also been reported in the literature. One of the goals of the next years will be to optimize the tissue and cell delivery of therapeutic molecules by means of peptides which combine both targeting and internalization advantages. In this review, we describe the main strategies that are currently in use or likely to be employed in the near future to associate both targeting and delivery properties.

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“…There is subsequent release of the entrapped drugs into the cytosol (Berg et al, 1999;Selbo et al, 2000a). PCI of numerous macromolecules has been demonstrated in vitro, including the 30-kDa ribosome-inactivating proteins gelonin and saporin (Berg et al, 1999), gelonin-and saporin-based targeting toxins (Selbo et al, 2000b;Weyergang et al, 2006), different peptide nucleic acids (Folini et al, 2003;Shiraishi and Nielsen, 2006), and DNA for gene therapeutic purposes both with viral and nonviral vectors (Hogset et al, 2004). Recently it was shown that using photosensitizers localizing to endocytic vesicles enhanced the delivery of adenoviruses to the nucleus after PCI treatment .…”

mentioning

confidence: 99%

Photochemical Internalization of Therapeutic Macromolecular Agents: A Novel Strategy to Kill Multidrug-Resistant Cancer Cells

Selbo¹,

Weyergang²,

Bonsted

et al. 2006

J Pharmacol Exp Ther

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Drug resistance is a major problem for chemotherapy. Entrapment of anticancer drugs in endolysosomal compartments or active extrusions by plasma membrane proteins of the ATPbinding cassette (ABC) superfamily are important resistance mechanisms. This study evaluated photochemical internalization (PCI) of membrane-impermeable macromolecules that are not the target of ABC drug pumps for treating multidrug-resistant (MDR) cancer cells. We used the drug-sensitive uterine fibrosarcoma cell line MES-SA and its MDR, P-glycoprotein (P-gp)-overexpressing derivative MES-SA/Dx5 with the photosensitizer disulfonated meso-tetraphenylporphine (TPPS 2a ) and broad spectrum illumination. The PCI of doxorubicin, the ribosome-inactivating protein gelonin and adenoviral transduction were assessed in both cell lines, together with the uptake and excretion of TPPS 2a and of two fluid phase markers easily detectable by fluorescence [lucifer yellow (LY) and fluorescein isothiocyanate (FITC)-dextran], as a model of gelonin uptake. Both cell lines were resistant to PCI of doxorubicin, but equally sensitive to PCI of gelonin, even though the endocytosis rates of LY and FITC-dextran were significantly lower in the MDR cells. In control studies, MES-SA/Dx5 cells were more resistant to photodynamic therapy (TPPS 2a ϩ light only). This was not mediated by P-gp, as there were no differences in the uptake and efflux of TPPS 2a between the cell lines. After adenoviral infection, PCI enhanced gene delivery in both cell lines. In conclusion, PCI of macromolecular therapeutic agents that are not targets of P-gp is a novel therapeutic strategy to kill MDR cancer cells.

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Photochemically enhanced cellular delivery of cell penetrating peptide‐PNA conjugates

Cited by 81 publications

References 16 publications

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Cell-penetrating and cell-targeting peptides in drug delivery

Photochemical Internalization of Therapeutic Macromolecular Agents: A Novel Strategy to Kill Multidrug-Resistant Cancer Cells

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