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Carbon Nanotubes for Drug Delivery Applications
Published in Ann Rose Abraham, Soney C. George, A. K. Haghi, Carbon Nanotubes, 2023
Jahanvee Mitra, G. K. P. Srilekha, Nilesh Wagh, Jaya Lakkakula
Earlier, it was discovered that cyclin A2 is a protein responsible for DNA replication, transcription, and regulating the cell cycle. On suppressing cyclin A2 by delivering siRNA, the proliferation of cancer cells can be controlled and apoptosis can be induced. Wang et al. applied the same strategy in their experiment by using functionalized single-walled CNTs mixed with siRNA (f-SWCNTs–siRNA), made out of a complementary strand of that of cyclin A2 producing gene. F-SWCNTs–siRNA of length 50–300 nm were analyzed by FT-IR and XPS and deployed for the treatment of chronic myelogenous leukemia cells (K562). Wang et al. reported that siRNA delivered by f-SWCNT was successful in suppressing cyclin A2 producing genes and eventually breaking the cycle of cancer cell division. This was one of the new strategies brought up by researchers in order to treat leukemia which is predicted to be used extensively in the coming future.71
Biomedical Applications IV: Carbon Nanotube-Nucleic Acid Complexes for Biosensors, Gene Delivery and Selective Cancer Therapy
Published in Giorgia Pastorin, carbon nanotubes, 2019
Makam Venkata Sudheer, Cang-Rong Jason Teng, Yoong Sia Lee, Pastorin Giorgia
An interesting target in gene therapy is represented by cyclin A2, a protein often over-expressed in many types of cancers, including leukemia. Since it was demonstrated to play a critical role in DNA replication, transcription and cell cycle regulation, it has been hypothesised that its selective inhibition through siRNA can be beneficial against tumour progression. To that purpose, Wang et al condensed ammonium-functionalised SWCNTs with cyclin A2 siRNA and incubated the complex in human myelogenous leukaemia (K562) cells.98 Results showed reduced cellular levels through blockage of cell proliferation in S phase as well as promotion of apoptosis. No analogous effects were measured with the controls. Similarly to Dai, the authors demonstrated that CNT transporters can efficiently deliver siRNA into cells and offer remarkable advantages with respect to conventional transfection vectors, which showed little effect in the internalisation of siRNA. On the basis of these encouraging results, together with the evidence that normal cells are less sensitive than transformed cells to siRNA,99 it could be envisaged that the delivery of siRNA against cyclin A2 mediated by functionalised SWCNTs is a useful therapeutic strategy for cancer therapy.
Phytoconstituents from Neem with Multiple Activities
Published in Bhupinder Singh, Om Prakash Katare, Eliana B. Souto, NanoAgroceuticals & NanoPhytoChemicals, 2018
Suman Chaudhary, Rupinder Kaur Kanwar, Teenu Sharma, Bhupinder Singh, Jagat Rakesh Kanwar
The bioactivity of neem seed oil is mainly attributed to its rich content of azadirachtin. Azadirachtin, along with nimbolide, exerts significant cytotoxic effects on the viability of the human cervical cancer cell line (HeLa). It induces p53-dependent p21 accumulation, along with cell-cycle arrest at the G0/G1 phase, and causes decrease in cell-cycle regulatory proteins including cyclin b, PCNA, and cyclin D1. Further, it causes modifications in the nuclear morphology and induces apoptotic signals via a mitochondrial pathway (Priyadarsini et al., 2010). However, both azadirachtin and nimbolide are capable of causing toxicity since a high dose of azadirachtin (LD50 > 5000 mg/kg bw) and intraperitoneal or intravenous administration of nimbolide can cause acute toxicity in experimental animals (Glinsukon et al., 1986; Raizada et al., 2001). Another study, conducted on the bioinsecticide azadirachtin A, indicated that it is not genotoxic and has an antiproliferative effect on the Chinese hamster ovary cells (CHO) and on human lymphocytes. It modulates the first and second (M1 and M2) division metaphases, thus interfering with the cell-cycle progression (Mosesso et al., 2012). Nonetheless, extensive investigations are required on the precise molecular mechanisms, pharmacokinetics, and toxicity of these neem limonoids to explore the therapeutic and preventive potential of neem in humans.
Exposure to long-term evolution radiofrequency electromagnetic fields decreases neuroblastoma cell proliferation via Akt/mTOR-mediated cellular senescence
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Ju Hwan Kim, Sangbong Jeon, Hyung-Do Choi, Jae-Hun Lee, Jun-Sang Bae, Nam Kim, Hyung-Gun Kim, Kyu-Bong Kim, Hak Rim Kim
The cyclins bind to CDKs and then form cyclin-CDK complexes that predominantly regulate cell cycle progression (Wade Harper et al. 1993). Abbas and Dutta (2009) reported that CDK4 mainly controls the G1 phase, and that CDK2 and CDK1 regulate the S and M phases, respectively. To examine whether the rise in cyclin-CDK inhibitors p21 and p27 might be associated with the delay in G0/G1 following RF-EMF exposure, the protein expression levels of CDK1, CDK2, CDK4, and cyclin D were determined in SH-SY5Y cells. The protein expression levels of CDK2, CDK4, and cyclin D were significantly decreased after RF-EMF exposure (Figure 6b–d), with no marked change in CDK1 protein expression (Figure 6a).