Lyophilized HER2-specific PEGylated immunoliposomes for active siRNA gene silencing

Gao, Jie; Sun, Jing; Li, Huimei; Liu, Wei; Zhang, Yang; Li, Bohua; Qian, Weizhu; Wang, Hao; Chen, Jianming; Guo, Yajun

doi:10.1016/j.biomaterials.2009.11.112

Cited by 88 publications

(65 citation statements)

References 36 publications

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“…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. 22 PEGylation also reduces the cytotoxicity and pH sensitivity of complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes.…”

Section: Resultssupporting

confidence: 93%

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: Resultssupporting

confidence: 93%

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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“…Several antibodies, including anti-human epidermal growth factor receptor 2 (HER2) or anti-epidermal growth factor receptor (EGFR) antibodies, have been used to promote the delivery of small interfering RNA nanoparticles to EGFR-overexpressing or HER2-overexpressing cancers (18,19). As cluster of differentiation (CD)133 is considered to be a marker for ovarian CSCs, our group hypothesized that the CD133 antibody may be able to promote the salinomycin delivery of nanoparticles to CD133-overexpressing ovarian CSCs.…”

Section: The Enhanced Delivery Of Salinomycin To Cd133 + Ovarian Cancmentioning

confidence: 99%

The enhanced delivery of salinomycin to CD133+ ovarian cancer stem cells through CD133 antibody conjugation with poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles

Huang

Deng

2018

Oncol Lett

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Abstract. Ovarian cancer is the most lethal gynecologic malignancy, and ovarian cancer stem cells (CSCs) serve a pivotal function in the metastasis and recurrence of ovarian cancer. Multiple previous studies have validated CD133 as a marker of ovarian CSCs. Although salinomycin is a promising therapeutic agent that has been demonstrated to kill CSCs in various types of cancer, poor aqueous solubility hampers its clinical application. The present study used salinomycin-loaded poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles conjugated with CD133 antibodies (CD133-SAL-NP) to eliminate CD133 + ovarian CSCs. The results revealed that CD133-SAL-NPs were of an appropriate size (149.2 nm) and exhibited sustained drug release. CD133-SAL-NPs efficiently bound to CD133 + ovarian cancer cells, resulting in an increased cytotoxic effect in CD133 + ovarian cancer cells, compared with the untargeted SAL-NPs and salinomycin. CD133-SAL-NPs reduced the percentage of CD133 + ovarian CSCs in ovarian cells more effectively than treatment with salinomycin or SAL-NPs, suggesting that CD133-SAL-NP targeted CD133 + ovarian CSCs. In nude mice bearing ovarian cancer xenografts, CD133-SAL-NPs exerted improved therapeutic effects compared with SAL-NPs and salinomycin. Thus, CD133 was demonstrated to be a promising target for drug delivery to ovarian CSCs, and may be useful as an agent to inhibit the growth of ovarian cancer by targeting CD133 + ovarian CSCs. CD133-SAL-NPs may therefore represent a promising approach for the treatment of ovarian cancer.

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“…27,28 DOTAP-CLs, composed of DOTAP/Chol/DSPE-mPEG (10:7.5:1 molar ratio, 7 μmol); DC-Chol-CLs, composed of DC-Chol/DOPE/DSPE-mPEG (10:7.5:1 molar ratio, 7 μmol); and EPC-ALs (ALs), composed of EPC/Chol/ DSPE-mPEG (10:7.5:1 molar ratio, 7 μmol), were prepared by the lipid film hydration method. The lipid film was hydrated with 10 mM phosphate-buffered saline (PBS, pH 7.4) and then extruded into unilamellar liposomes with a hand-held extruder (Mini Extruder; Avanti Polar Lipids) using membranes with 200 nm pore sizes (Whatman ® Nuclepore™ membrane; Thermo Fisher Scientific) at room temperature.…”

Section: Preparation and Characterization Of Liposomesmentioning

confidence: 99%

Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens

Gao¹,

Ochyl²,

Yang³

et al. 2017

IJN

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Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation – the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8 + T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8 + T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8 + T-cells. To achieve this, we have used 3β-[ N -( N ′, N ′-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8 + T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials.

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Lyophilized HER2-specific PEGylated immunoliposomes for active siRNA gene silencing

Cited by 88 publications

References 36 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

The enhanced delivery of salinomycin to CD133+ ovarian cancer stem cells through CD133 antibody conjugation with poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles

Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens

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