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- 저자 : Othman Iekhsan (검색결과 2 건)
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( Chia Yuen Chong ),( Iekhsan Othman ),( Ezharul Hoque Chowdhury ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1
Background: The current conventional way of chemotherapy using anti-cancer drugs has caused many side effects to patients. There are a high number of patients reporting intolerable symptoms, including nausea and vomiting, tiredness, depression, and more that results in poor quality of life. This is mainly due to non-selective cytotoxic effect of anticancer drugs that not only kill the cancer cells, but also affect the normal healthy cells. Eventually, these unbearable adverse effects increase the number of patients abandoning treatment, and in some others delaying their treatment progress. The pH sensitive carbonate apatite (CA), a major component of hard tissues in the body, has evolved as an effi cient non-viral inorganic DNA nanocarrier. Due to heterogenous charge distribution and being armed with ability to prevent crystal growth for generation of nanoscale particles, CA nanoparticles offer an ideal way to deliver anticancer drugs to targeted cancer cells via endocytosis. Methods: Bio-functionalized nanoparticles with loaded drugs were fabricated and characterized by measurement of particle size, zeta potential and drug binding affi nity. Breast cancer cell lines, MCF-7 and 4T1 were cultured, maintained and seeded in a 24- well plate. Drug-loaded CA particles were incubated with the seeded cells for 48 hours before analysis of cell viability by MTT assay. Results: We found that cell treatment with drug-loaded CA particles have lower cell viability in comparison to cell treatment with only free drugs. And this result is consistent in all different drug concentrations being tested. Conclusions: It is likely that the CA has a promising future for clinical cancer treatment in increasing the effectiveness of chemotherapy and concurrently reducing its side effect.
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Haque Sheikh Tanzina,Karim Md. Emranul,Othman Iekhsan,Chowdhury Ezharul Hoque 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.3
In this work, pH-sensitive alpha-ketoglutaric acid-modified Fe/Mg-carbonate apatite (α-KAM-Fe/Mg-CA) NPs were introduced and found to be capable of promoting the selective delivery of cancer-killing drug doxorubicin (DOX) in breast cancer cells, while simultaneously mitigating DOX toxicity on normal cells.As part of the characterization and evaluation of α-KAM-Fe/Mg-CA NPs to target breast cancer cells, a series of assessments were performed, which included size measurements, morphological analysis, FTIR, cytotoxicity assessment, hemolysis, drug binding, cellular uptake, and pH-responsive drug release tests. Liquid chromatography-mass spectrometry was used to conduct the protein corona analysis of α-KAM-Fe/Mg-CA using 10% FBS (fetal bovine serum) and mice plasma. Furthermore, to investigate the distribution of DOX-loaded α-KAM-Fe/Mg-CA NPs in major tissues and the tumor, a biodistribution investigation was conducted in mammary tumor-induced Balb/c mouse models 24 h after the intravenous administration of DOX-loaded α-KAM-Fe/Mg-CA NPs.The in vitro pH-dependent release of DOX over time demonstrated that α-KAM-Fe/Mg-CA NPs were pH-responsive and degraded rapidly at acidic pH levels. When compared to free DOX, the DOX-loaded α-KAM-Fe/Mg-CA NPs demonstrated a potent antiproliferative effect on breast cancer cells. Confocal microscopy confirmed the effective internalization of DOX-loaded α-KAM-Fe/Mg-CA NPs in breast cancer cells. The protein corona analysis revealed an affinity for dysopsonins (serum albumin, apolipoproteins) and transport proteins that may assist in extending their blood circulation period. Furthermore, biodistribution data of DOX-loaded α-KAM-Fe/Mg-CA NPs in the mammary tumor-induced Balb/c mouse model indicated extended circulation in the bloodstream, reduced non-target distribution in major tissues, and increased drug accumulation in the tumor.The results obtained suggest that α-KAM-Fe/Mg-CA NPs may emerge as a prospective candidate for delivering therapeutic cargos to treat malignant mammary tumors.
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