Dual-Targeted Therapy in HER2-Overexpressing Breast Cancer with Trastuzumab and Novel Cholesterol-Based Nioplexes Silencing Mcl-1

The challenge in HER2-overexpressing breast cancer therapy lies in creating an effective target therapy to overcome treatment resistance. Monoclonal antibodies and target gene silencing by siRNA are two potential strategies that have been widely developed for treating HER2-positive breast cancer. Th...

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Main Authors: Supusson Pengnam (Author), Praneet Opanasopit (Author), Theerasak Rojanarata (Author), Boon-ek Yingyongnarongkul (Author), Chopaka Thongbamrer (Author), Samarwadee Plianwong (Author)
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Publicado em: MDPI AG, 2023-10-01T00:00:00Z.
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100 1 0 |a Supusson Pengnam  |e author 
700 1 0 |a Praneet Opanasopit  |e author 
700 1 0 |a Theerasak Rojanarata  |e author 
700 1 0 |a Boon-ek Yingyongnarongkul  |e author 
700 1 0 |a Chopaka Thongbamrer  |e author 
700 1 0 |a Samarwadee Plianwong  |e author 
245 0 0 |a Dual-Targeted Therapy in HER2-Overexpressing Breast Cancer with Trastuzumab and Novel Cholesterol-Based Nioplexes Silencing Mcl-1 
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500 |a 10.3390/pharmaceutics15102424 
500 |a 1999-4923 
520 |a The challenge in HER2-overexpressing breast cancer therapy lies in creating an effective target therapy to overcome treatment resistance. Monoclonal antibodies and target gene silencing by siRNA are two potential strategies that have been widely developed for treating HER2-positive breast cancer. The siRNA delivery system is a crucial factor that influences siRNA therapy's success. In this study, lipid-based nanoparticles (cationic niosomes) composed of different cholesterol-based cationic lipids were formulated and characterized for delivering siRNA into HER2-overexpressing breast cancer cells. Niosomes containing a trimethylammonium headgroup showed the highest siRNA delivery efficiency with low toxicity. The myeloid cell leukemia-1 (Mcl-1) siRNA nioplex treatment significantly decreased mRNA expression and breast cancer cell growth. Dual-targeted therapy, consisting of treatment with an Mcl-1 siRNA nioplex and trastuzumab (TZ) solution, noticeably promoted cell-growth inhibition and apoptosis. The synergistic effect of dual therapy was also demonstrated by computer modeling software (CompuSyn version 1.0). These findings suggest that the developed cationic niosomes were effective nanocarriers for siRNA delivery in breast cancer cells. Furthermore, the Mcl-1 nioplex/TZ dual treatment establishes a synergistic outcome that may have the potential to treat HER2-overexpressing breast cancer. 
546 |a EN 
690 |a HER2-overexpressing breast cancer 
690 |a lipid nanoparticles 
690 |a niosomes 
690 |a siRNA therapy 
690 |a dual therapy 
690 |a Pharmacy and materia medica 
690 |a RS1-441 
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786 0 |n Pharmaceutics, Vol 15, Iss 10, p 2424 (2023) 
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