Rap2b siRNA significantly enhances the anticancer therapeutic efficacy of Adriamycin in a gold nanoshell-based drug/gene co-delivery system

Ding, Li; Sun, Rong; Zhang, Xinyue

doi:10.18632/oncotarget.15508

Cited by 11 publications

(13 citation statements)

References 47 publications

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“…GNSs are potential nanotechnology‐based drug delivery systems that can accommodate 1 or more active drugs of nano‐size to be dispersed, absorbed, conjugated or encapsulated and thereby targeted to be released in, for example, skin cancer or specific organs. Several experimental studies have implemented GNS in drug delivery, for example, by attaching GNS to anticancer antibodies . The increased intensity of GNS in OCT images makes it a potential candidate for use as a carrier in targeted drug delivery systems monitored by OCT.…”

Section: Discussionmentioning

confidence: 99%

Two optical coherence tomography systems detect topical gold nanoshells in hair follicles, sweat ducts and measure epidermis

Mogensen

Bojesen

Israelsen

et al. 2018

Journal of Biophotonics

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Optical coherence tomography (OCT) is an established imaging technology for in vivo skin investigation. Topical application of gold nanoshells (GNS) provides contrast enhancement in OCT by generating a strong hyperreflective signal from hair follicles and sweat glands, which are the natural skin openings. This study explores the utility of 150 nm diameter GNS as contrast agent for OCT imaging. GNS was massaged into skin and examined in four skin areas of 11 healthy volunteers. A commercial OCT system and a prototype with 3 μm resolution (UHR-OCT) were employed to detect potential benefits of increased resolution and variability in intensity generated by the GNS. In both OCT-systems GNS enhanced contrast from hair follicles and sweat ducts. Highest average penetration depth of GNS was in armpit 0.64 mm ± SD 0.17, maximum penetration depth was 1.20 mm in hair follicles and 15 to 40 μm in sweat ducts. Pixel intensity generated from GNS in hair follicles was significantly higher in UHR-OCT images (P = .002) and epidermal thickness significantly lower 0.14 vs 0.16 mm (P = .027). This study suggests that GNSs are interesting candidates for increasing sensitivity in OCT diagnosis of hair and sweat gland disorders and demonstrates that choice of OCT systems influences results.

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Section: Discussionmentioning

confidence: 99%

Two optical coherence tomography systems detect topical gold nanoshells in hair follicles, sweat ducts and measure epidermis

Mogensen

Bojesen

Israelsen

et al. 2018

Journal of Biophotonics

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“…31 In addition, Ding et al designed a nanostructure-based drug and siRNA delivery system to knock down the expression of Rap2b, a novel p53 target, enhancing adriamycin-based anticancer therapeutics. 32 Furthermore, the use of a novel liposome to efficiently deliver siRNA against MGMT, a DNA repair protein, promoted temozolomide cytotoxicity, 33 and the strategy of simultaneously co-delivering epirubicin and BCL-2 siRNA with lipid-NPs significantly reversed tumor cell multidrug resistance. 34 In summary, these combined therapies provide an experimental basis for their use to reduce clinical drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy

Wu¹,

Wang²,

Zhang³

et al. 2018

IJN

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PurposeFTY720, known as fingolimod, is a new immunosuppressive agent with effective anticancer properties. Although it was recently confirmed that FTY720 inhibits cancer cell proliferation, FTY720 can also induce protective autophagy and reduce cytotoxicity. Blocking autophagy with Beclin 1 siRNA after treatment with FTY720 promotes apoptosis. The objective of this study was to enhance the anticancer effect of FTY720 in hepatocellular carcinoma (HCC) by targeted co-delivery of FTY720 and Beclin 1 siRNA using calcium phosphate (CaP) nanoparticles (NPs).Materials and methodsFirst, the siRNA was encapsulated within the CaP core. To form an asymmetric lipid bilayer structure, we then used an anionic lipid for the inner leaflet and a cationic lipid for the outer leaflet; after removing chloroform by rotary evaporation, these lipids were dispersed in a saline solution with FTY720. The NPs were analyzed by transmission electron microscopy, dynamic light scattering and ultraviolet–visible spectrophotometry. Cancer cell viability and cell death were analyzed by MTT assays, fluorescence-activated cell sorting analysis and Western blotting. In addition, the in vivo effects of the NPs were investigated using an athymic nude mouse subcutaneous transplantation tumor model.ResultsWhen the CaP NPs, called LCP-II NPs, were loaded with FTY720 and siRNA, they exhibited the expected size and were internalized by cells. These NPs were stable in systemic circulation. Furthermore, co-delivery of FTY720 and Beclin 1 siRNA significantly increased cytotoxicity in vitro and in vivo compared with that caused by treatment with the free drug alone.ConclusionThe CaP NP system can be further developed for co-delivery of FTY720 and Beclin 1 siRNA to treat HCC, enhancing the anticancer efficacy of FTY720. Our findings provide a new insight into HCC treatment with co-delivered small molecules and siRNA, and these results can be readily translated into cancer clinical trials.

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“…Reactions were run in a CFX96 Touch™ Real-time PCR system (Bio-Rad Laboratories, Hercules, USA) and data were analyzed using the built-in CFX Manager™ software. Data normalization was performed as previously described [ 26 , 27 ]. The primer sequences are listed in Supplementary Table S1 .…”

Section: Methodsmentioning

confidence: 99%

Ribosomal L1 domain-containing protein 1 coordinates with HDM2 to negatively regulate p53 in human colorectal Cancer cells

Ding

Zhang

Zhao

et al. 2021

J Exp Clin Cancer Res

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Background Ribosomal L1 domain-containing protein 1 (RSL1D1) is a nucleolar protein that is essential in cell proliferation. In the current opinion, RSL1D1 translocates to the nucleoplasm under nucleolar stress and inhibits the E3 ligase activity of HDM2 via direct interaction, thereby leading to stabilization of p53. Methods Gene knockdown was achieved in HCT116p53+/+, HCT116p53−/−, and HCT-8 human colorectal cancer (CRC) cells by siRNA transfection. A lentiviral expression system was used to establish cell strains overexpressing genes of interest. The mRNA and protein levels in cells were evaluated by qRT-PCR and western blot analyses. Cell proliferation, cell cycle, and cell apoptosis were determined by MTT, PI staining, and Annexin V-FITC/PI double staining assays, respectively. The level of ubiquitinated p53 protein was assessed by IP. The protein-RNA interaction was investigated by RIP. The subcellular localization of proteins of interest was determined by IFA. Protein-protein interaction was investigated by GST-pulldown, BiFC, and co-IP assays. The therapeutic efficacy of RSL1D1 silencing on tumor growth was evaluated in HCT116 tumor-bearing nude mice. Results RSL1D1 distributed throughout the nucleus in human CRC cells. Silencing of RSL1D1 gene induced cell cycle arrest at G1/S and cell apoptosis in a p53-dependent manner. RSL1D1 directly interacted with and recruited p53 to HDM2 to form a ternary RSL1D1/HDM2/p53 protein complex and thereby enhanced p53 ubiquitination and degradation, leading to a decrease in the protein level of p53. Destruction of the ternary complex increased the level of p53 protein. RSL1D1 also indirectly decreased the protein level of p53 by stabilizing HDM2 mRNA. Consequently, the negative regulation of p53 by RSL1D1 facilitated cell proliferation and survival and downregulation of RSL1D1 remarkably inhibited the growth of HCT116p53+/+ tumors in a nude mouse model. Conclusion We report, for the first time, that RSL1D1 is a novel negative regulator of p53 in human CRC cells and more importantly, a potential molecular target for anticancer drug development.

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Rap2b siRNA significantly enhances the anticancer therapeutic efficacy of Adriamycin in a gold nanoshell-based drug/gene co-delivery system

Cited by 11 publications

References 47 publications

Two optical coherence tomography systems detect topical gold nanoshells in hair follicles, sweat ducts and measure epidermis

Two optical coherence tomography systems detect topical gold nanoshells in hair follicles, sweat ducts and measure epidermis

Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy

Ribosomal L1 domain-containing protein 1 coordinates with HDM2 to negatively regulate p53 in human colorectal Cancer cells

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