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Review on telomerase activity in metastasis and proposal of amino-modified polystyrene-antisense human RNA nanoparticles in killing metastatic cells

Ching Ho Szeto

Abstract


Telomeres protect chromosomes from losing base-pair sequences at their ends. Part of telomeres is lost during each cell division. When the telomere becomes too short, the chromosome can no longer replicate. Telomerase, by reverse transcription, maintains telomere length and stability in cancer, gonadal and hemopoietic stem cells. During telomerase maturation, the RNA component is transferred to the cytoplasm where it recruits proteins and the mature complex is then re-imported into the nucleus. Telomerase activity in cancer cells is 10-20 times greater than that in normal cells.

Amino silica nanoparticles are transport carrier for antisense human telomerase RNA (hTR) to cytoplasm where hTR binds to telomerase mRNA leading to its degradation. Sometimes anti-telomerase leads to growth arrest but not to cancerous cell death.

It is proposed that amino polystyrene (NH2PS) can replace amino silica nanoparticles and carry antisense hTR to the cytoplasm. After the binding of the antisense hTR to the mRNA of telomerase, NH2PS nanoparticles will be released. These nanoparticles  inhibit the mammalian target of rapamycin (mTOR) signaling, leading to G2 cell cycle arrest of all cells exhibiting activated mTOR signaling including cancer cells. Due to the absence of mTOR signaling, macrophage resist to NH2PS toxicity. Besides, NH2PS inhibits angiogenesis and proliferation of tumour cells.


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