Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery

Xiang, Dongxi; Shigdar, Sarah; Bean, Andrew G.D.; Bruce, Matthew P.; Yang, Wenrong; Mathesh, Motilal; Wang, Tao; Wang, Yin; Tran, Phuong Ha Lien; Shamaileh, Hadi Al; Barrero, Roberto A.; Zhang, Pei Zhuo; Li, Yong; Kong, Lingxue; Liu, Ke; Zhou, Shu Feng; Hou, Yingchun; He, Aina; Duan, Wei

doi:10.7150/thno.20168

Cited by 73 publications

(52 citation statements)

References 77 publications

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“…These conjugates have been produced by either covalent or noncovalent conjugation through intercalation . Through self‐assembly by noncovalent integration of doxorubicin into engineered DNA–RNA hybrid EpCAM aptamer, this drug‐aptamer conjugate was able to effectively target colorectal CSCs, internalize and deliver the drug to the nuclei of CSCs in vivo . In addition, Duan lab pioneered aptamer‐guided in vivo delivery of siRNA into CSCs by engineering a chimera of EpCAM aptamer and a 27 mer Dicer substrate survivin siRNA ( Figure A–F).…”

Section: Aptamer Emerges As a Prominent Targeting Ligand For Nanodelimentioning

confidence: 99%

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

et al. 2019

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Intense efforts from both scientists and physicians across Australia have been devoted onward advancing studies to fill the gap in understanding the biology and pathogenesis underlying cancer development. Exosomes are membrane-bound bio-nanoparticles secreted or released by most cells into the extracellular space. There has been an increasing interest in such bio-nanoparticles over the past 10 years, evident from the publication number of only 324 papers in 2006 to a massive increase to 4603 publications in 2018 with the search term "exosome" based on title/abstract in PubMed. Among these studies, 151 articles published from 2007 to 2018 are from Australian institutions, with 33 papers published in 2018. Such a strong surge of interest is due to discoveries that exosomes play key roles in intercellular and intertissue communication mediated by virtue of cargos contained inside the membrane-confined space. Furthermore, exosome cargos, including proteins, mRNAs and miRNAs, are linked to the Targeted exosomal delivery systems for precision nanomedicine attract wide interest across areas of molecular cell biology, pharmaceutical sciences, and nanoengineering. Exosomes are naturally derived 50-150 nm nanovesicles that play important roles in cell-to-cell and/or cell-to-tissue communications and cross-species communication. Exosomes are also a promising class of novel drug delivery vehicles owing to their ability to shield their payload from chemical and enzymatic degradations as well as to evade recognition by and subsequent removal by the immune system. Combined with a new class of affinity ligands known as aptamers or chemical antibodies, molecularly targeted exosomes are poised to become the next generation of smartly engineered nanovesicles for precision medicine. Here, recent advances in targeted exosomal delivery systems engineered by aptamer for future strategies to promote human health using this class of human-derived nanovesicles are summarized.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.

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Section: Aptamer Emerges As a Prominent Targeting Ligand For Nanodelimentioning

confidence: 99%

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

et al. 2019

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“…We interrogated CMap utilizing the gene expression signatures from SHH MB samples with high and low mRNAsi levels. The CMap analysis precisely identified some compounds that have been shown to specifically impact CSCs in other tumor types (Angeletti et al, 2016;Batsaikhan et al, 2014;Battula et al, 2017;Bonuccelli et al, 2017;Bozok Cetintas et al, 2016;Chen et al, 2015Chen et al, , 2016Cheng et al, 2017;Dominguez-Gomez et al, 2018;Garulli et al, 2014;Hong et al, 2011;Hou et al, 2018;Malkomes et al, 2016;Xiang et al, 2017;Xu et al, 2016;Yeh et al, 2013;Yin et al, 2018;You et al, 2009;Zhang et al, 2013;Zheng et al, 2013a,b). These compounds include the CDK inhibitors palbociclib and alvocidib, the AMPK inhibitor dorsomorphin, the IKK inhibitor BMS-345541, the smoothened receptor antagonist cyclopamine, the topoisomerase inhibitors topotecan and doxorubicin, the GABA receptor agonist ivermectin, the NF-jB pathway inhibitor auranofin, the MTOR inhibitor dactolisib, the AKT inhibitors MK-2206 and pyrvinium-pamoate, the HMGCR inhibitor simvastatin, the HDAC inhibitors apicidin, vorinostat, and givinostat, and the DNA synthesis inhibitor anisomycin.…”

Section: Correlation Of the Immune Cells With Mdnasimentioning

confidence: 99%

Integrative analysis of gene expression and DNA methylation through one‐class logistic regression machine learning identifies stemness features in medulloblastoma

et al. 2019

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Most human cancers develop from stem and progenitor cell populations through the sequential accumulation of various genetic and epigenetic alterations. Cancer stem cells have been identified from medulloblastoma (MB), but a comprehensive understanding of MB stemness, including the interactions between the tumor immune microenvironment and MB stemness, is lacking. Here, we employed a trained stemness index model based on an existent one‐class logistic regression (OCLR) machine‐learning method to score MB samples; we then obtained two stemness indices, a gene expression‐based stemness index (mRNAsi) and a DNA methylation‐based stemness index (mDNAsi), to perform an integrated analysis of MB stemness in a cohort of primary cancer samples (n = 763). We observed an inverse trend between mRNAsi and mDNAsi for MB subgroup and metastatic status. By applying the univariable Cox regression analysis, we found that mRNAsi significantly correlated with overall survival (OS) for all MB patients, whereas mDNAsi had no significant association with OS for all MB patients. In addition, by combining the Lasso‐penalized Cox regression machine‐learning approach with univariate and multivariate Cox regression analyses, we identified a stemness‐related gene expression signature that accurately predicted survival in patients with Sonic hedgehog (SHH) MB. Furthermore, positive correlations between mRNAsi and prognostic copy number aberrations in SHH MB, including MYCN amplifications and GLI2 amplifications, were detected. Analyses of the immune microenvironment revealed unanticipated correlations of MB stemness with infiltrating immune cells. Lastly, using the Connectivity Map, we identified potential drugs targeting the MB stemness signature. Our findings based on stemness indices might advance the development of objective diagnostic tools for quantitating MB stemness and lead to novel biomarkers that predict the survival of patients with MB or the efficacy of strategies targeting MB stem cells.

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“…The microbiota seems to include a variety of bacterial species and many of them have yet to be characterized. Nevertheless, the bacterial pathogens leading to inflammatory disorders have one thing in common; they all employ several mechanisms to overcome the human immune cells and are hard to be removed naturally …”

Section: Biofilm and Chronic Inflammatory Diseasementioning

confidence: 99%

The biofilm‐associated bacterial infections unrelated to indwelling devices

et al. 2020

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Biofilms are microbial communities established in the self‐produced extracellular substances that include up to 80% of associated microbial infections. During biofilm formation, bacterial cells shift from the planktonic forms to aggregated forms surrounded by an extracellular polymeric substance. The bacterial biofilm shows resistance against immune reactions as well as antibiotics and is potentially able to cause disorders by both device‐related and nondevice‐related infections. The nondevice‐related bacterial biofilm infections include dental plaque, urinary tract infections, cystic fibrosis, otitis media, infective endocarditis, tonsillitis, periodontitis, necrotizing fasciitis, osteomyelitis, infectious kidney stones, and chronic inflammatory diseases. In this review, we will summarize and examine the literature about bacterial biofilm infections unrelated to indwelling devices.

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Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery

Cited by 73 publications

References 77 publications

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

Integrative analysis of gene expression and DNA methylation through one‐class logistic regression machine learning identifies stemness features in medulloblastoma

The biofilm‐associated bacterial infections unrelated to indwelling devices

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