pH-sensitive immunoliposomes specific to the CD33 cell surface antigen of leukemic cells

Simard, Pierre; Leroux, Jean‐Christophe

doi:10.1016/j.ijpharm.2009.05.013

Cited by 58 publications

(38 citation statements)

References 79 publications

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“…In this regard, our results are consistent with previous reports. 11,12 PEGylation is a signif icant modif ication strategy for improving the stability and extending the lifetime of liposomes in vivo. 21 However, our results show that PEGylation, although reducing the size and surface charge density of liposomes, can significantly reduce the pDNA transfection efficiency of complexes of DC-Chol/ DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes, which is consistent with a previous report.…”

Section: Resultsmentioning

confidence: 99%

“…10 However, the gene transfection efficiency of pH-sensitive liposomes remains unsatisfactory, 11,12 with numerous pH-sensitive liposomes showing low transfection efficiency in the presence of serum. For example, Legendre et al reported that cationic liposomes achieved only transient transfection in their experimental cell lines, whereas pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and DOPE at a 2/1 molar ratio mediated gene transfer with an efficiency that was 1%-30% of that obtained using cationic liposomes.…”

Section: Introductionmentioning

confidence: 99%

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Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

Chen

Ji²,

Lü³

et al. 2013

IJN

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pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfection efficiency of pH-sensitive liposomes, we prepared complexes containing 3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidyl ethanolamine (DOPE) liposomes and pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and DOPE, and evaluated the influence of various factors on plasmid DNA (pDNA) transfection efficiency. All DC-Chol/DOPE liposome/pDNA and pH-sensitive liposome complexes showed similarly potent pH sensitivity. In the presence of serum-containing medium, two optimized complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes showed high transfection efficiency of 22.94% and 20.07%, respectively. Notably, DC-Chol/DOPE (2:3) liposomes/pH-sensitive PEGylated (1%) liposome complexes with a charge ratio of 1:1 (m/m [+/−]) showed enhanced accumulation in tumors in vivo. Our results show the influence of various factors on pDNA transfection efficiency in complexes of DC-Chol/DOPE liposomes and pH-sensitive PEGylated liposomes. Understanding of such mechanisms will lead to better design of complexes of DC-Chol/DOPE liposomes and pH-sensitive liposomes for gene therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

Chen

Ji²,

Lü³

et al. 2013

IJN

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“…The intracellular delivery of cytotoxic drugs by the pH-sensitive liposomes presents an efficient means of overcoming the multidrug resistance, one of the causes for cancer treatment failures. Further, the anchoring of site-directing ligands on such pH-sensitive liposomes potentiates the effect by targeted drug delivery (Simard & Leroux, 2009.…”

Section: The Ph-sensitive Liposomes In Drug Deliverymentioning

confidence: 99%

A review of mechanistic insight and application of pH-sensitive liposomes in drug delivery

2014

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The pH-sensitive liposomes have been extensively used as an alternative to conventional liposomes in effective intracellular delivery of therapeutics/antigen/DNA/diagnostics to various compartments of the target cell. Such liposomes are destabilized under acidic conditions of the endocytotic pathway as they usually contain pH-sensitive lipid components. Therefore, the encapsulated content is delivered into the intracellular bio-environment through destabilization or its fusion with the endosomal membrane. The therapeutic efficacy of pHsensitive liposomes enables them as biomaterial with commercial utility especially in cancer treatment. In addition, targeting ligands including antibodies can be anchored on the surface of pH-sensitive liposomes to target specific cell surface receptors/antigen present on tumor cells. These vesicles have also been widely explored for antigen delivery and serve as immunological adjuvant to enhance the immune response to antigens. The present review deals with recent research updates on application of pH-sensitive liposomes in chemotherapy/ diagnostics/antigen/gene delivery etc.

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“…As a potential long circulation candidate for siRNA delivery, pH-sensitive PEG-lipid has been proven to assist to reduce liposome surface protein absorption and aggregation to extend halflife and release siRNA into cytoplasm. 54 High transfection efficiency does not always mean superior gene silencing activity because enough siRNA escape from endosome/ lysosome is required. Upon release of FAM-siRNA from EPSLR into cytoplasm, the cellular fluorescence is expected to increase significantly ( Figure 7D).…”

mentioning

confidence: 99%

Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA

Zang¹,

Ding²,

Zhao³

et al. 2016

IJN

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Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Here, a pH-sensitive cholesterol–Schiff base–polyethylene glycol (Chol–SIB–PEG)-modified cationic liposome–siRNA complex, conjugated with the recombinant humanized anti-EphA10 antibody (Eph), was developed as an efficient nonviral siRNA delivery system. Chol–SIB–PEG was successfully synthesized and confirmed with FTIR and 1 H-NMR. An Eph–PEG–SIB–Chol-modified liposome–siRNA complex (EPSLR) was prepared and characterized by size, zeta potential, gel retardation, and encapsulation efficiency. Electrophoresis results showed that EPSLR was resistant to heparin replacement and protected siRNA from fetal bovine serum digestion. EPSLR exhibited only minor cytotoxicity in MCF-7/ADR cells. The results of flow cytometry and confocal laser scanning microscopy suggested that EPSLR enhanced siRNA transfection in MCF-7/ADR cells. Intracellular distribution experiment revealed that EPSLR could escape from the endo-lysosomal organelle and release siRNA into cytoplasm at 4 hours posttransfection. Western blot experiment demonstrated that EPSLR was able to significantly reduce the levels of MDR1 protein in MCF-7/ADR cells. The in vivo study of DIR-labeled complexes in mice bearing MCF-7/ADR tumor indicated that EPSLR could reach the tumor site rather than other organs more effectively. All these results demonstrate that EPSLR has much potential for effective siRNA delivery and may facilitate its therapeutic application.

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pH-sensitive immunoliposomes specific to the CD33 cell surface antigen of leukemic cells

Cited by 58 publications

References 79 publications

Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

A review of mechanistic insight and application of pH-sensitive liposomes in drug delivery

Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA

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