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RISS 인기검색어
- 검색키워드
- 저자 : Athirah Bakhtiar (검색결과 3 건)
- 무료
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Bakhtiar Athirah,Liew Qing Xin,Ng Khuen Yen,Chowdhury Ezharul Hoque 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.2
Purpose Gene therapy is a promising and novel therapeutic strategy for many mutated gene-associated diseases, including breast cancer. However, it poses significant biological drawbacks such as rapid clearance from the circulatory system and low cellular uptake of the exogenously delivered functional nucleic acids. The development of efficient and biocompatible carriers for genetic materials has been extensively explored in the literature, and the functionalization of nanoparticles (NPs) with cancer cell-recognizing ligands has become an attractive approach to promote tumor targetability and efficient cellular internalization via endocytosis. Methods This study introduced self-assembling targeting ligands, including transferrin and fibronectin with the ability to electrostatically interact with strontium nanoparticles (SNPs), and then analyzed their influence on size and zeta potential of the resultant hybrid SNPs, cellular uptake and expression efficiency of transgene-loaded hybrid NPs. Results Smaller ligand-coated SNPs (LCSNPs) remarkably increased gene transfection activity in both MCF-7 and 4T1 cells as well as nucleic acid localization into tumor tissues with improved tumor regression activity in a 4T1-tumor xenograft mouse model. Conclusion LCSNPs-mediated delivery of p53 gene and MAPK siRNA provided a proof-of-concept for the functionalized nanocarrier formulation in order to inhibit breast cancer cell growth.
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Bakhtiar Athirah,Neah Aik Seng,Ng Khuen Yen,Chowdhury Ezharul Hoque 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.1
Purpose Low efficacy of parenteral administration of naked therapeutic genes is associated with the presence of biological barriers including circulatory monocytes that clear and eliminate foreign materials via reticuloendothelial system. Chemically synthesized inorganic strontium nanoparticles (SNPs) present a way to improve the delivery of genetic content to the targeted tissues of mammary carcinoma while protecting the load from premature degradation. Methods Biodistribution profiles in the brain, liver, spleen, kidneys, lung, and mammary tumor of BALB/c mice were investigated at 1, 2 and 4 h following intravenous administration of fluorescent siRNA-loaded SNPs. Following SNPs-mediated in vivo delivery of p53 gene and MAPK siRNA, the effects of exogenous p53 expression and silencing of endogenous MAPK were analyzed via tumor size measurement over 14 days. Results SNPs mainly accumulate in the liver and kidney with notable deposition in the brain, lung, spleen, and tumor tissues. However, higher salt concentrations hindered the optimal localization of SNPs in tumor tissues. Despite lower residual accumulation in tumor tissues, mice treated with SNPs carrying either p53 gene or MAPK siRNA demonstrated slower tumor growth than those treated with the naked gene or siRNA. Unlike p53 gene, higher siRNA concentration resulted in lower regression activity of the carcinoma tissues, which might be due to unexpected off-target effects. Conclusion The effective role of SNPs in overcoming biological barriers in vivo and supporting gene trafficking for substantial nucleic acid activities at the targeted tissues provides an opportunity for future novel therapeutic strategies for breast cancer.
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Scope and challenges of nanoparticle-based mRNA delivery in cancer treatment
Md. Emranul Karim,Sheikh Tanzina Haque,Hamed Al-Busaidi,Athirah Bakhtiar,Kyi Kyi Tha,Mark M. Banaszak Holl,Ezharul Hoque Chowdhury 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.12
Messenger RNA (mRNA) recently emerged asan appealing alternative to treat and prevent diseases rangingfrom cancer and Alzheimer’s disease to COVID-19 withsignifi cant clinical outputs. The in vitro-transcribed mRNAhas been engineered to mimic the structure of natural mRNAfor vaccination, cancer immunotherapy and protein replacementtherapy. In past decades, signifi cant progress has beennoticed in unveiling the molecular pathways of mRNA,controlling its translatability and stability, and its evolutionarydefense mechanism. However, numerous unsolvedstructural, biological, and technical diffi culties hamper thesuccessful implementation of systemic delivery of mRNAfor safer human consumption. Advances in designing and manufacturing mRNA and selecting innovative deliveryvehicles are mandatory to address the unresolved issuesand achieve the full potential of mRNA drugs. Despite thesubstantial eff orts made to improve the intracellular deliveryof mRNA drugs, challenges associated with diverse applicationsin diff erent routes still exist. This study examines thecurrent progress of mRNA therapeutics and advancementsin designing biomaterials and delivery strategies, the existingtranslational challenges of clinical tractability and theprospects of overcoming any challenges related to mRNA.
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