Enhancement of cancer therapy efficacy by trastuzumab-conjugated and pH-sensitive nanocapsules with the simultaneous encapsulation of hydrophilic and hydrophobic compounds |
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| Institution: | 1. Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu, Taiwan;2. Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan;3. Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan;1. Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina (UNC) Eshelman School of Pharmacy, Chapel Hill, NC, USA;3. Department of Mathematics, Carlow University, Pittsburgh, Pennsylvania;4. The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA;5. Molecular Therapeutics, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA;6. UNC GLP Bioanalytical Facility, Chapel Hill, NC, USA;7. Institute for Pharmacogenomics and Individualized Therapy (IPIT), Chapel Hill, NC, USA;8. Carolina Center of Cancer Nanotechnology Excellence (C-CCNE), Chapel Hill, NC, USA;9. North Carolina Biomedical Innovation Network (NC BIN), Chapel Hill, NC, USA;10. Duquesne University Mylan School of Pharmacy;1. Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School of Southeast University, Nanjing 210009, China;2. School of Public Health, Southeast University, Nanjing 210009, China;1. Department of Biomedical Engineering, SRM University, Kattankulathur, Chennai 603203, India;2. SRM Research Institute, SRM University, Kattankulathur, Chennai 603203, India |
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| Abstract: | Trastuzumab-conjugated pH-sensitive double emulsion nanocapsules (DENCs) stabilized by a single-component Poly (vinyl alcohol) (PVA) with magnetic nanoparticles can be fabricated through a two-step double emulsion process; these nanocapsules can be used to encapsulate hydrophilic doxorubicin (Dox) and hydrophobic paclitaxel (PTX) simultaneously. When PMASH was attached to the shell of the DENCs, enhanced dual drug release of PTX/Dox was detected, specifically in intracellular acidic pH environments. The targeting ability of these Trastuzumab-conjugated DENCs was demonstrated with confocal images, which revealed a significantly elevated cellular uptake in HER-2 overexpressing SkBr3 cells. More importantly, an intravenous injection of this co-delivery system followed by magnetic targeting (MT) chemotherapy suppressed cancer growth in vivo more efficiently than the delivery of either PTX or Dox alone. The integration of the functionalities makes this combination therapy system a powerfully new tool for in vitro/in vivo cancer therapy, especially for in HER-2 positive cancers.From the Clinical EditorTrastuzumab-conjugated pH-sensitive nanocapsules were used in this study for simultaneous targeted delivery of hydrophobic (PTX) and hydrophilic (Dox) anti-cancer agents to HER-2 positive cancer cells. Additional use of magnetic targeting demonstrated superior efficacy of this delivery system compared to PTX or Dox alone. |
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