The promotion of siRNA delivery to breast cancer overexpressing epidermal growth factor receptor through anti-EGFR antibody conjugation by immunoliposomes

Gao, Jie; Liu, Wei; Xia, Yu; Li, Wei; Sun, Jing; Chen, Huaiwen; Li, Bohua; Zhang, David; Qian, Weizhu; Meng, Yanchun; Deng, Li; Wang, Hao; Chen, Jianming; Guo, Yajun

doi:10.1016/j.biomaterials.2011.01.034

Cited by 112 publications

(56 citation statements)

References 31 publications

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“…It could be due to steric hindrance of PEGylation, electric hindrance, or the adverse effect of antibody modification on encapsulation efficiency. 43 The results of the gel retardation assay ( Figure 3A) showed that the siRNA in EPSLR was fully complexed at an N/P ratio of 5, which was consistent with the encapsulation efficiency results.…”

Section: Gel Retardation Assaysupporting

confidence: 83%

“…Meanwhile, serum incubation with LR complexes resulted in a significantly lower siRNA degradation ratio (stable for 5 hours), which was attributed to the siRNA that was only bound to the outer surface of liposomes, and would immediately release and be degraded by nucleases. 43 The siRNA in EPSLR and PSLR showed the best integrity, which was visualized even after 24 hours incubation, suggesting that EPSLR and PSLR complexes provided a significant protection for siRNA against RNase degradation compared to LR. The serum stability assay demonstrated that EPSLR could significantly increase siRNA stability, which was likely due to the presence of the PEGylated shell and the anti-EphA10 antibody that sterically hampered the access of nucleases to siRNA.…”

mentioning

confidence: 93%

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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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Section: Gel Retardation Assaysupporting

confidence: 83%

mentioning

confidence: 93%

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

Zang¹,

Ding²,

Zhao³

et al. 2016

IJN

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“…Because TEM was used to measure the dehydrated diameter of the NPs, while the laser particle size analyzer determined their hydrodynamic diameter, there was a slight difference in size between the results of the TEM and DLS analyses, as previously reported. [32][33][34] The zeta potentials of the RPM NPs and RPM/siRNA were negative. In general, negatively charged particles are taken up less efficiently by cells, and they are therefore not an obvious choice for use as siRNA carriers, though they have occasionally been employed for siRNA delivery.…”

Section: Discussionmentioning

confidence: 99%

Self-assembled nanoparticles based on the c(RGDfk) peptide for the delivery of siRNA targeting the VEGFR2 gene for tumor therapy

Liu¹,

Liu²,

Xu³

et al. 2014

IJN

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The clinical application of small interfering RNA (siRNA) has been restricted by their poor intracellular uptake, low serum stability, and inability to target specific cells. During the last several decades, a great deal of effort has been devoted to exploring materials for siRNA delivery. In this study, biodegradable, tumor-targeted, self-assembled peptide nanoparticles consisting of cyclo(Arg–Gly–Asp–d–Phe–Lys)-8–amino–3,6–dioxaoctanoic acid–β–maleimidopropionic acid (hereafter referred to as RPM) were found to be an effective siRNA carrier both in vitro and in vivo. The nanoparticles were characterized based on transmission electron microscopy, circular dichroism spectra, and dynamic light scattering. In vitro analyses showed that the RPM/VEGFR2-siRNA exhibited negligible cytotoxicity and induced effective gene silencing. Delivery of the RPM/VEGFR2 (zebrafish)-siRNA into zebrafish embryos resulted in inhibition of neovascularization. Administration of RPM/VEGFR2 (mouse)-siRNA to tumor-bearing nude mice led to a significant inhibition of tumor growth, a marked reduction of vessels, and a down-regulation of VEGFR2 (messenger RNA and protein) in tumor tissue. Furthermore, the levels of IFN-α, IFN-γ, IL-12, and IL-6 in mouse serum, assayed via enzyme-linked immunosorbent assay, did not indicate any immunogenicity of the RPM/VEGFR2 (mouse)-siRNA in vivo. In conclusion, RPM may provide a safe and effective delivery vector for the clinical application of siRNAs in tumor therapy.

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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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The promotion of siRNA delivery to breast cancer overexpressing epidermal growth factor receptor through anti-EGFR antibody conjugation by immunoliposomes

Cited by 112 publications

References 31 publications

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

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

Self-assembled nanoparticles based on the c(RGDfk) peptide for the delivery of siRNA targeting the VEGFR2 gene for tumor therapy

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

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The promotion of siRNA delivery to breast cancer overexpressing epidermal growth factor receptor through anti-EGFR antibody conjugation by immunoliposomes

Cited by 112 publications

References 31 publications

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

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

Self-assembled nanoparticles based on the c(RGDfk) peptide for the delivery of siRNA targeting the VEGFR2&nbsp;gene for tumor therapy

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

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Self-assembled nanoparticles based on the c(RGDfk) peptide for the delivery of siRNA targeting the VEGFR2 gene for tumor therapy