Lipo-oligoarginines as effective delivery vectors to promote cellular uptake

Lee, Jae Sam; Tung, Ching–Hsuan

doi:10.1039/c004684a

Cited by 32 publications

(41 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several small, punctuated spots were observed in the cytoplasmic membrane of cells treated with AMLPs, indicating that multiple pathways might be involved during cellular uptake and intracellular trafficking. [31, 43] Calcein red-orange fluorescence images further demonstrated the lack of cellular toxicity of fAuNPs (Figure 4C; cell viability). There were no significant differences in calcein red-orange cellular fluorescence between AuNPs and fAuNPs.…”

Section: Resultsmentioning

confidence: 90%

“…Since the cell fixation process could cause artifacts in the intracellular distribution of cargo molecules, all microscopic observations were conducted in live cells. [31, 42] Confocal microscopic images showed FITC and calcein red-orange were distributed inside the Jurkat cells (Figure 4). FITC fluorescence, which corresponded to FITC molecules conjugated to AALPs or AMLPs, was evenly distributed in the plasma membrane and cytoplasm (Figure 4B; intracellular distribution).…”

Section: Resultsmentioning

confidence: 99%

“…AuNPs (20 nm, Ted Pella Inc., Redding, CA) were functionalized by conjugating acetylated oligoarginine (acetyl-dR11; ALP) or myristoylated oligoarginine (myristoyl-dR11; MLP), which were synthesized as reported previously [30, 31]. Detailed information is available online in the Methods of the Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

“…[30–32] One particular LOAP, myristoylated hendeca-D-arginine peptide (MLP, Figure 1), exhibited the most reliable results for elevated cellular uptake rate, intracellular localization, low cellular toxicity, and enhanced metabolic stability. [31] Therefore, we prepared functionalized AuNPs (fAuNPs) by incorporating MLP on their surfaces to improve cellular uptake rate and intracellular trafficking with minimal cellular toxicity. For comparison, acetylated hendeca-D-arginine peptides (ALP, Figure 1) were included as a control and to study the contribution of the lipophilic myristoyl group.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Enhancing the Cellular Delivery of Nanoparticles Using Lipo‐Oligoarginine Peptides

Lee

Tung

2012

Adv Funct Materials

Self Cite

View full text Add to dashboard Cite

Nanoparticles have great potential as nanotherapeutics, delivery vectors, and molecular imaging agents due to their flexible properties. Although intracellular and nuclear delivery of nanoparticles is desirable for therapeutic applications, it remains a challenge. Cell penetrating peptides (CPPs) are a powerful tool for the intracellular delivery of various cargoes. Here we report that functionalization of nanoparticles with a myristoylated oligoarginine CPP promoted cellular uptake without increased toxicity. It was evidenced that the myristoylated CPP is much more effective in transporting nanoparticles than the unmodified CPPs.

show abstract

Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enhancing the Cellular Delivery of Nanoparticles Using Lipo‐Oligoarginine Peptides

Lee

Tung

2012

Adv Funct Materials

Self Cite

View full text Add to dashboard Cite

show abstract

“…Tracking rhodamine B uptake is an efficient way to quantify liposomal uptake rates. The cationic guanidine group of the arginine side chain has previously been shown to be important for the membrane translocation properties, 29 and might have enhanced the internalization of PA functionalized liposomes. 1).…”

Section: In Vitro Uptake Of Model Dyes Entrapped In Liposomesmentioning

confidence: 99%

Cell penetrating peptide amphiphile integrated liposomal systems for enhanced delivery of anticancer drugs to tumor cells

et al. 2013

View full text Add to dashboard Cite

Liposomes have been extensively used as effective nanocarriers, providing better solubility, higher stability and slower release of drugs compared to free drug administration. They are also preferred due to their nontoxic nature as well as their biodegradability and cell membrane mimicking abilities. In this study, we examined noncovalent integration of a cell penetrating arginine-rich peptide amphiphile into a liposomal formulation of negatively charged 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DOPG) phospholipids in the presence of cholesterol due to its amphipathic character. We studied changes in the physical characteristics (size, surface potential and membrane polarity) of the liposomal membrane, as well as in the encapsulation of hydrophilic and hydrophobic agents due to peptide amphiphile incorporation. The activities of peptide integrated liposomal systems as drug delivery agents were investigated by using anticancer drugs, doxorubicin-HCI and paclitaxel. Enhancement in liposomal uptake due to arginine-rich peptide integration, and enhanced efficacy of the drugs were observed with peptide functionalized liposomes compared to free drugs.

show abstract

Enhanced cellular uptake and metabolic stability of lipo‐oligoarginine peptides

Lee

Tung

2011

Biopolymers

Self Cite

View full text Add to dashboard Cite

Developing efficient cellular delivery vectors is crucial for designing novel therapeutic agents to enhance their plasma membrane permeability and metabolic stability in cells. Previously, we engineered cell penetrating peptide vectors named as “lipo-oligoarginine peptides” (LOAPs) by conjugating a proper combination of fatty acid and oligoarginine that translocated into cell easily without adverse effect on cell viability. In the present study, we report a systemic evaluation of cellular uptake and metabolic stability of LOAPs in Jurkat cells by introducing different combination of D-Arg residues in the peptide backbone. The cellular uptake and intracellular fate, cell viability, and metabolic stability and proteolytic degradation patterns of various LOAPs consisted of different combination of L- and D-Arg sequences were confirmed by flow cytometry, cytotoxicity assay, and analytical RP-HPLC with MALDI-TOF mass. All investigated LOAPs penetrated the cell efficiently with low cellular toxicity. The LOAPs having D-Arg residues at their N-termini seemed to have better metabolic stability than the LOAPs having C-terminal D-Arg residues. The metabolic degradation patterns were similar among all investigated LOAPs. The major hydrolytic site was between lauroyl group and β-Ala residue. Without the lipid chain, the oligoarginine peptide was pumped out of cells easily. The results presented in this study suggest that structurally modified LOAPs could be used as a novel CPP design toward improved therapeutic application.

show abstract

Lipo-oligoarginines as effective delivery vectors to promote cellular uptake

Cited by 32 publications

References 39 publications

Enhancing the Cellular Delivery of Nanoparticles Using Lipo‐Oligoarginine Peptides

Enhancing the Cellular Delivery of Nanoparticles Using Lipo‐Oligoarginine Peptides

Cell penetrating peptide amphiphile integrated liposomal systems for enhanced delivery of anticancer drugs to tumor cells

Enhanced cellular uptake and metabolic stability of lipo‐oligoarginine peptides

Contact Info

Product

Resources

About