Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides

Gupta, Bhawna; Levchenko, Tatiana S; Torchilin, Vladimir P.

doi:10.1016/j.addr.2004.10.007

Cited by 598 publications

(502 citation statements)

References 117 publications

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“…Studies using Tat-nanoparticles or Tat-liposomes suggest that the translocation mechanism occurs via energy-dependent macropinocytosis [43] and [49], whereas peptide-conjugated small molecules penetrate via electrostatic interactions and do not seem to depend on energy [50]. The exact mechanism of protamine-mediated penetration of microparticles into non-phagocytic cells remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Gómez

Csaba

Fischer

et al. 2008

Journal of Controlled Release

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Surface modifications of poly(lactide-co-glycolide) microparticles with different polycationic electrolytes have mainly been studied for conjugation to antigens and/or adjuvants. However, the in vivo immunological effects of using surface charged particles have not been address yet. In this study, microparticles were coated or not with protamine, a cationic and arginine-rich electrolyte that confers microparticles with a positively surface charge. We then evaluated the potential of protamine-coatings to assist the induction of immune responses in mice. Interestingly, enhanced antibodies and T-cell responses were observed in mice treated with the coated particles. In vitro studies suggested that the improved immunological performance was mediated by an increased uptake. Indeed, protamine-coated particles that carried a plasmid were even internalised into non-phagocytic cells and to cause their transfection. These results open the way for further research into a novel technology that combines the use protamine for facilitated cell penetration of that and biodegradable microparticles for prolonged antigen or drug release.

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Section: Discussionmentioning

confidence: 99%

Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Gómez

Csaba

Fischer

et al. 2008

Journal of Controlled Release

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“…These are bilayer-based nanospheres with sizes ranging from ∼50 to 300 nm. Currently, liposomes are widely used for drug delivery purposes (Gupta et al, 2005), including intracellular drug and gene delivery (Rao and Gopal, 2006;Serpe et al, 2006). Many aspects related to the detailed mechanisms of the liposome-to-cell interaction remain unresolved.…”

Section: Label Free Imaging Of Cellular Mitochondrial Distribution-thismentioning

confidence: 99%

“…Many aspects related to the detailed mechanisms of the liposome-to-cell interaction remain unresolved. This is especially true for the case of liposomal nanocarriers modified by cellpenetrating peptides, such as the HIV-1 trans-activating transcriptional activator-derived TAT peptide (Gupta et al, 2005). These carrier systems are currently considered a very promising way to bring various drugs, including protein and peptides, into cells (Wadia and Dowdy, 2005).…”

Section: Label Free Imaging Of Cellular Mitochondrial Distribution-thismentioning

confidence: 99%

Chapter 10 Infrared and Raman Microscopy in Cell Biology

Matthäus

Bird

Miljković

et al. 2008

Methods in Cell Biology

165

119

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This chapter presents novel microscopic methods to monitor cell biological processes of live or fixed cells without the use of any dye, stains, or other contrast agent. These methods are based on spectral techniques that detect inherent spectroscopic properties of biochemical constituents of cells, or parts thereof. Two different modalities have been developed for this task. One of them is infrared micro-spectroscopy, in which an average snapshot of a cell's biochemical composition is collected at a spatial resolution of typically 25 mm. This technique, which is extremely sensitive and can collect such a snapshot in fractions of a second, is particularly suited for studying gross biochemical changes. The other technique, Raman microscopy (also known as Raman microspectroscopy), is ideally suited to study variations of cellular composition on the scale of subcellular organelles, since its spatial resolution is as good as that of fluorescence microscopy. Both techniques exhibit the fingerprint sensitivity of vibrational spectroscopy toward biochemical composition, and can be used to follow a variety of cellular processes.

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“…Organ or tissue (tumor, infarct) accumulation could be achieved by the passive targeting via the enhanced permeability and retention (EPR) effect (1,2); or by the antibody-mediated active targeting (3,4), while the intracellular delivery could be mediated by certain internalizable ligands (folate, transferrin) (5,6) or by cell-penetrating peptides (CPPs, such as TAT or polyArg) (7,8). Such a DDS should simultaneously carry on its surface various active moieties, i.e.…”

Section: Introductionmentioning

confidence: 99%

“SMART” Drug Delivery Systems: Double-Targeted pH-Responsive Pharmaceutical Nanocarriers

et al. 2006

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In order to develop targeted pharmaceutical carriers additionally capable of responding certain local stimuli, such as decreased pH values in tumors or infarcts, targeted long-circulating PEGylated liposomes and PEG-phosphatidylethanolamine (PEG-PE)-based micelles have been prepared with several functions. First, they are capable of targeting a specific cell or organ by attaching the monoclonal antimyosin antibody 2G4 to their surface via pNP-PEG-PE moieties. Second, these liposomes and micelles were additionally modified with biotin or TAT peptide (TATp) moieties attached to the surface of the nanocarrier by using biotin-PE or TATp-PE or TATp-short PEG-PE derivatives. PEG-PE used for liposome surface modification or for micelle preparation was made degradable by inserting the pH-sensitive hydrazone bond between PEG and PE (PEG-Hz-PE). Under normal pH values, biotin and TATp functions on the surface of nanocarriers were "shielded" by long protecting PEG chains (pH-degradable PEG 2000 -PE or PEG 5000 -PE) or by even longer pNP-PEG-PE moieties used to attach antibodies to the nanocarrier (non-pH-degradable PEG 3400 -PE or PEG 5000 -PE). At pH 7.5-8.0, both liposomes and micelles demonstrated high specific binding with 2G4 antibody substrate, myosin, but very limited binding on an avidin column (biotin-containing nanocarriers) or internalization by NIH/3T3 or U-87 cells (TATp-containing nanocarriers). However, upon brief incubation (15-to-30 min) at lower pH values (pH 5.0-6.0) nanocarriers lost their protective PEG shell because of acidic hydrolysis of PEG-Hz-PE and acquired the ability to become strongly retained on avidin-column (biotin-containing nanocarriers) or effectively internalized by cells via TATp moieties (TATp-containing nanocarriers). We consider this result as the first step in the development of multifunctional stimuli-sensitive pharmaceutical nanocarriers.

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Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides

Cited by 598 publications

References 117 publications

Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Chapter 10 Infrared and Raman Microscopy in Cell Biology

“SMART” Drug Delivery Systems: Double-Targeted pH-Responsive Pharmaceutical Nanocarriers

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