pH‐sensitive liposomes mediate cytoplasmic delivery of encapsulated macromolecules

Straubinger, Robert M.; Düzgüneş, Nejat; Papahadjopoulos, Demetrios

doi:10.1016/0014-5793(85)80210-6

Cited by 233 publications

(79 citation statements)

References 27 publications

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“…This does not dispute with the reported advantages of the 'pH-sensitive' liposomes, but rather points out relatively low efficiency in cytosolic delivery of macromolecules 38 when pH-sensitive liposomes do not carry an additional endosomolytic mechanism for release into the cytosol such as that provided by LLO in our study.…”

Section: Discussionsupporting

confidence: 59%

Cytosolic delivery of antisense oligonucleotides by listeriolysin O-containing liposomes

Mathew

et al. 2003

Gene Ther

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Antisense oligodeoxynucleotides (ODNs) possess great potential as sequence-specific therapeutic agents. Sufficient concentrations of intact ODN must bypass membrane barriers and access the cytosol and nucleus, for ODNs to be therapeutically effective. A cytosolic delivery strategy was designed to improve the efficiency of ODN delivery in bone-marrow-derived macrophages. This liposome-based formulation utilizes listeriolysin O (LLO), the endosomolytic hemolysin from Listeria monocytogenes, to mediate the escape of ODN from endocytic compartments into the cytosol. To monitor the cytosolic delivery of ODN, subcellular trafficking of fluorescently labeled ODNs was visualized using epifluorescence microscopy. The expression of target protein and mRNA after delivery was measured using flow cytometry and Northern blot analysis, respectively. ODN specific for murine intercellular adhesion molecule-1 (ICAM-1) encapsulated in LLO-liposomes was released to the cytosol and trafficked to the nucleus, efficiently and specifically suppressing activation-induced expression of ICAM-1 at both protein and mRNA levels. Delivery without LLO resulted in sequestration of ODN in vesicular compartments leading to little inhibition of ICAM-1 expression, which supports the requirement of LLO for efficient cytosolic delivery using this system. The data clearly demonstrate that LLO-mediated escape of ODN from intracellular vesicles is an effective approach to achieve full therapeutic antisense activity in cultured macrophages.

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Section: Discussionsupporting

confidence: 59%

Cytosolic delivery of antisense oligonucleotides by listeriolysin O-containing liposomes

Mathew

et al. 2003

Gene Ther

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“…These results demonstrate that: (i) the extent of liposome internalization is a crucial step in the process of intracellular delivery and (ii) receptor-mediated endocytosis is more efficient than non-specific endocytosis. Nevertheless, although nonpH-sensitive immunoliposomes (containing PC instead of DOPE) are internalized as extensively as pH-sensitive immunoliposomes, their capacity to mediate cytoplasmic delivery of the encapsulated molecules is significantly lower [32,33]. These observations suggest that fusion or destabilization of liposomes induced by acidification of the endosomal lumen represents the most important stage in the process of intracellular delivery.…”

Section: Binding and Cell Internalizationmentioning

confidence: 99%

On the formulation of pH-sensitive liposomes with long circulation times

Simões

Moreira

Fonseca

et al. 2004

Advanced Drug Delivery Reviews

436

244

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Strategies used to enhance liposome-mediated drug delivery in vivo include the enhancement of stability and circulation time in the bloodstream, targeting to specific tissues or cells, and facilitation of intracytoplasmic delivery. pH-sensitive liposomes have been developed to mediate the introduction of highly hydrophilic molecules or macromolecules into the cytoplasm. These liposomes destabilize under acidic conditions found in the endocytotic pathway, and usually contain phosphatidylethanolamine (PE) and titratable stabilizing amphiphiles. Formulations without PE have also been developed. Encapsulated compounds are thought to be transported into the cytoplasm through destabilization of or fusion with the endosome membrane. Incorporation of a low mole percentage of poly(ethylene glycol) (PEG)-conjugated lipids into pHsensitive liposomes confers prolonged circulation times to these liposomes, which are otherwise cleared rapidly. While the incorporation of PEG -lipids reduces the pH-dependent release of encapsulated fluorescent markers in vitro, it does not hinder the cytoplasmic delivery of the markers per cell-associated liposome. This suggests that intracellular delivery is not dictated simply by the destabilization of the liposomes. Antibodies or ligands to cell surface receptors can be coupled to pH-sensitive or sterically stabilized pH-sensitive liposomes for targeting. pH-sensitive liposomes have been used to deliver anticancer drugs, antibiotics, antisense oligonucleotides, ribozymes, plasmids, proteins and peptides to cells in culture or in vivo. D

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“…pH-Sensitive liposomes composed of phosphatidylethanolamine (DOPE) were protonated in endosomes/lysosomes, which stimulated the release of drug cargos into the cytoplasm. 1,2) Later, a series of ionizable aminolipids were synthesized and utilized for nucleic acid delivery to the liver and to tumors as a formulation of stable nucleic acid-lipid particles (SNALPs) or ionizable lipid nano particles (iLNPs). [3][4][5][6] Recently, we designed a new pH-sensitive cationic lipid, YSK05 (1-methyl-4,4-biz[(9Z,12Z )-octadeca-9,12-dien-1-yloxy]-piperidine).…”

Section: Activation In Response To Endogenous/internal Stimulimentioning

confidence: 99%

Recent Advances in Endogenous and Exogenous Stimuli-Responsive Nanocarriers for Drug Delivery and Therapeutics

Hatakeyama

2017

Chem. Pharm. Bull.

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Significant progress has been achieved in the development of stimuli-responsive nanocarriers for drug delivery, diagnosis, and therapy. Various types of triggers are utilized in the development of nanocarrier delivery. Endogenous factors such as changes in pH, redox, gradient, and enzyme concentration which are linked to disease progression have been utilized for controlling biodistribution and releasing drugs from nanocarriers, as well as increasing subsequent pharmacological activity at the disease site. Nanocarriers which respond to artificially-induced exogenous factors (such as temperature, light, magnetic field, and ultrasound) have also been developed. This review aims to discuss recent advances in the design of stimuliresponsive nanocarriers which appear to have a promising future in medicine.

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pH‐sensitive liposomes mediate cytoplasmic delivery of encapsulated macromolecules

Cited by 233 publications

References 27 publications

Cytosolic delivery of antisense oligonucleotides by listeriolysin O-containing liposomes

Cytosolic delivery of antisense oligonucleotides by listeriolysin O-containing liposomes

On the formulation of pH-sensitive liposomes with long circulation times

Recent Advances in Endogenous and Exogenous Stimuli-Responsive Nanocarriers for Drug Delivery and Therapeutics

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