Journal
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 17, Issue 3, Pages 447-455Publisher
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2021.3043
Keywords
Anti-HER2 Single-Chain Fv Fragment Decorated DM1 Nanoparticles; Trastuzumab-Decorated DM1 Nanoparticles; Cellular Uptake; Biodistribution Study; In Vivo Antitumor Activity; HER2-Positive Breast Tumor
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The study demonstrates that DM1 nanoparticles decorated with anti-HER2 single-chain Fv fragment can effectively target HER2-overexpressing breast cancer cells, showing better antitumor effects compared to traditional monoclonal antibody-decorated nanoparticles. This approach could potentially be developed into a novel drug delivery system for HER2-positive breast cancer treatment.
Purpose: Although monoclonal antibodies are used to decorate nanoparticles to target specific cells, penetration of tumor tissues by monoclonal antibodies is limited by their large size. Therefore, we prepared DM1 nanoparticles decorated with the small anti-HER2 single-chain Fv fragment (scFvHER2) of trastuzumab (TMAB) for targeting to human epidermal growth factor receptor 2 (HER2) overexpressing in breast cancer effectively. Methods: ScFvHER2 fragment was coupled with DM1 nanoparticles (NPs) via covalent thiol-maleimide linkages. Their physicochemical properties, uptake by cells, and toxicity to tumor cells were investigated. Their vivo biodistribution was assessed employing liquid chromatographytandem mass spectrometry, while their antitumor activity was investigated in nude mice burdened with BT-474 tumor. Results: Viability of BT-474 cells incubated with scFvHER2-DM1-Nanoparticles (scFv-DM1-NPs) was significantly lower than that of BT-474 cell treated with TMAB-DM1-Nanoparticles (TMAB-DM1-NPs) (P < 0.05). Uptake by cells of scFv-DM1-NPs was significantly higher than TMAB-DM1-NPs (P < 0.01). Accumulation of scFv-DM1-NPs in tumor tissue was notably higher than TMAB-DM1-NPs (P < 0.05). scFv-DM1-NPs exhibited improved antitumor effects compared to TMAB-DM1-NPs (P < 0.05), showing a tumor inhibition rate of more than 70%. Conclusions: ScFvHER2 fragment could serve as a more effective targeting ligand than TMAB, and scFv-DM1-NPs could be developed as a possible drug delivery system to target HER2-positive breast cancer.
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