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Nanomedicine Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Saima Zulfiqar, Zunaira Naeem, Shahzad Sharif, Ayoub Rashid Ch., M. Zia-Ul-Haq, Marius Moga
A suitable nanocarrier selection can eliminate many limitations in drug delivery, for example, toxic auristatin conjugates for hematological cancer treatment with the disadvantage of less drug pay-loads. This limitation was solved with the development of polymeric nanoparticles giving advantage of high drug (auristatin) payload for effective tumor repression [97]. Intolerable side effects of Aurora B kinase observed in a trial phase were avoided by combining it with polyethylene glycol/polylactide nanoparticles. Moreover, nucleic acid containing drugs also face limitations associated with intracellular delivery and unstable system of circulation [98–101]. Formulation of lipid nanoparticles loaded with nucleic acid drugs eliminated its conventional limitations with the aid of targeting the liver [102]. Similarly, silica mesopo-rous nanoparticles coated with lipid offered advantages of biocompatibility and more time for systematic circulation for the delivery of an antiviral drug, ML336. A high through output method, FIND was also reported, which screen these lipid nanoparticles for the in vivo delivery promoting nanocarriers as “immuno-oncology” therapeutics with the elimination of associated toxicity [103–105].
Nanomaterials in COVID-19 Drug Development
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Alaa A. A. Aljabali, Ángel Serrano-Aroca, Kenneth Lundstrom, Murtaza M. Tambuwala
The formulation of nanoparticles made from poly(ethylene glycol)–poly(lactide) with an inhibitor of Aurora B demonstrated increased efficacy and decreased toxicity as contrasted to their free form, which in phase II clinical trials developed intolerable side effects [40]. Lipid-based siRNA nanoparticles are just an illustration of a nanotechnology tool (Onpattro) to prevent systemic breakdown and benefit liver targeting. For example, encapsulation of the ML336 antiviral compound in lipid-coated mesoporous silica nanoparticles resulted in extended circulation time and demonstrated inhibition of Venezuelan equine encephalitis virus (VEE) in vivo [41]. In the screening of LNPs that can bypass the liver and provide functional mRNA to cells in vivo, Dahlman et al. [33] reported a high-performance approach (called FIND). This approach can be used widely to elucidate the relations between nanoparticles’ arrangement, and mRNA in vivo delivery targets. Nanocarriers are used for the prevention of protein-based systemic immunotoxicity and facilitate immuno-oncology treatment [42].
Targeting Subgroup-specific Cancer Epitopes for Effective Treatment of Pediatric Medulloblastoma
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sidharth Mahapatra, Naveenkumar Perumall
Aurora kinase A and B maintain genomic stability through their involvement in chromosome separation during mitosis [95]. Overexpression has been shown to lead to oncogenesis in multiple types of cancers, aside from medulloblastoma [96]. Aurora kinase A (AURKA) inhibition was shown to induce apoptosis in DAOY cells and to lead to a time-dependent G2/M phase arrest [97]. Moreover, AURKA inhibition reduced the IC„ of etoposide and cisplatin concurrently enhancing their cytotoxic effects in vitro [97]. Aurora kinase B (Aurora B) co-expression has been shown specifically in the high MYC-expressing group 3 tumors. Inhibition of Aurora B in MYC overexpressing cells not only reduced tumor cell proliferation but also sensitized them to apoptosis [98]. In MB xenograft models, Aurora B inhibition impaired cerebellar tumor growth and augmented survival [98].
Emerging cell cycle inhibitors for treating metastatic castration-resistant prostate cancer
Published in Expert Opinion on Emerging Drugs, 2018
Aurora kinases are serine/threonine kinases that play major roles in mitosis and cytokinesis. Aurora A localizes to the centrosomes starting in S phase and is essential for centrosome maturation, spindle assembly, and spindle orientation [19]. Overexpression of Aurora A causes inactivation of the DNA damage checkpoint during the G2 phase [81] and inactivation of the spindle assembly checkpoint during mitosis [82]. This leads to tetraploidy and centrosome amplification, especially in cells with the defective p53-dependent DNA damage checkpoint [83]. Aurora kinase A has been implicated as an androgen-regulated AR target gene, especially in the context of highly AR-expressing CRPC. In a preclinical study, AR binds to the regulatory region of the Aurora kinase A gene and its transcript was upregulated in a prostate cancer model [84]. Other analyses of human tumors support oncogenic roles for Aurora A and Aurora B.
Aurora kinase A as a possible marker for endocrine resistance in early estrogen receptor positive breast cancer
Published in Acta Oncologica, 2018
Anne E. Lykkesfeldt, Benedikte R. Iversen, Maj-Britt Jensen, Bent Ejlertsen, Anita Giobbie-Hurder, Birgit E. Reiter, Tove Kirkegaard, Birgitte B. Rasmussen
Studies of cell culture models mimicking ER positive breast cancer resistant to the antiestrogens tamoxifen and fulvestrant and also to aromatase inhibitors have disclosed that Aurora kinases are important for growth of both antiestrogen and aromatase inhibitor resistant breast cancer cells [2–4]. Aurora kinases (A, B and C) are key regulators of mitosis and multiple signaling pathways [5,6]. Gene amplification and protein overexpression of Aurora kinases have been found in both hematologic malignancies and solid tumors and deregulation of Aurora kinases has been linked to tumorigenesis [7]. Aurora A is consistently associated with cancers and Aurora B may also contribute to tumorigenesis, whereas the role of Aurora C is not yet clarified [8].
Ultra-long silver nanowires induced mitotic abnormalities and cytokinetic failure in A549 cells
Published in Nanotoxicology, 2019
Fengbang Wang, Ying Chen, Yuanyuan Wang, Yongguang Yin, Guangbo Qu, Maoyong Song, Hailin Wang
We used long-term time-lapse video microscopy to analyze mitotic events in the A549 cell line. By using this system, we were able to track the fate of progeny from multipolar mitosis and of cells that subsequently underwent multipolar mitosis. Interestingly, we observed that two daughter cells often remerged into one giant cell during cytokinesis (Figure 5(c)), indicating cytokinesis failure and multipolarity induced by AgNW treatment. Aurora B is a kinase located at the midzone during telophase and at the flanking regions of the midbody during cytokinesis (Hu, Coughlin, and Mitchison 2012). The inactivation of Aurora B can cause cytokinesis to progress and abscission to occur, but the activation of Aurora B inhibits the late stages of cytokinesis (Carmena 2008; Agromayor and Martin-Serrano 2013). Here we presumed direct physical contact with ultra-long AgNWs as an involved mechanistic explanation for cytokinesis failure. During telophase, A549 cells entered into cytokinesis while cells remained interconnected by an intercellular bridge with a phase-dense midbody at the center. After AgNWs treatment for 12 h, AgNWs, particularly AgNW30, were often observed in the intercellular bridge between two daughter cells and promoted the accumulation of Aurora B in the midbody (Figure 5(d)). This result indicates that ultra-long AgNWs may obstruct the contractile ring and inhibit abscission of the cytokinetic furrow. Although whether AgNWs directly interact with the midbody was not confirmed, cells with chrysotile fibers in the intercellular bridge could finish cytokinesis, delivering the fiber to one of the cells after severing the bridge at one point (Cortez et al. 2016).