標題: | Mixed Lanthanide Oxide Nanoparticles Coated with Alginate-Polydopamine as Multifunctional Nanovehicles for Dual Modality: Targeted Imaging and Chemotherapy |
作者: | Addisu, Kefyalew Dagnew Hsu, Wei-Hsin Hailemeskel, Balkew Zewge Andrgie, Abegaz Tizazu Chou, Hsiao-Ying Yuh, Chiou-Hwa Lai, Juin-Yih Tsai, Hsieh-Chih 生物科技學系 Department of Biological Science and Technology |
關鍵字: | Lanthanide;Tumor penetration;Polydopamine;Spheroids;Zebrafish;Theranostic |
公開日期: | 1-十月-2019 |
摘要: | Integrating anticancer drugs and diagnostic agents in a polymer nanosystem is an emerging and promising strategy for improving cancer treatment. However, the development of multifunctional nano articles (NPs) for an "all-in-one" platform characterized by specific targeting, therapeutic efficiency, and imaging feedback remains an unmet clinical need. In this study, pH-responsive mixed-lanthanide-based multifunctional NPs were fabricated based on simple metal ligand interactions for simultaneous cancer cell imaging and drug delivery. We investigated two new systems of alginate-polydopamine complexed with either terbium/europium or dysprosium/erbium oxide NPs (Tb/Eu@AlgPDA or Dy/Er@AlgPDA NPs). Tb/Eu@AlgPDA NPs were then functionalized with the tumor-targeting ligand folic acid (FA) and loaded with the anticancer drug doxorubicin (DOX) to form FA-Tb/Eu@AlgPDA-DOX NPs. Using such systems, the mussel-inspired property of PDA was introduced to improve tumor targetability and penetration, in addition to active targeting (via FA-folate receptor interactions). Determining the photoluminescence efficiency showed that the Tb/Eu@AlgPDA system was superior to the Dy/Er@AlgPDA system, presenting intense and sharp emission peaks on the fluorescence spectra. In addition, compared to Dy/Er@A1gPDA NPs (82.4%), Tb/Eu@AlgPDA NPs exhibited negligible cytotoxicity with >93.3% HeLa cell viability found in MTT assays at NP concentrations of up to 0.50 mg/mL and high biocompatibility when incubated with zebrafish (Danio rerio) embryos and larvae. The FA-Tb/Eu@AlgPDA-DOX system exhibited a pH-responsive and sustained drug-release pattern. In a spheroid model of HeLa cells, the FA-Tb/Eu@AlgPDA-DOX system showed a better penetration efficiency and spheroid growth-inhibitory effect than free DOX. After incubation with zebrafish embryos, the FA-Tb/Eu@AlgPDA-DOX system also showed improved antitumor efficacies versus the other experimental groups in HeLa tumor cell xenografted zebrafish. Therefore, our results suggested that FA-Tb/Eu@AlgPDA-DOX NPs are promising multifunctional nanocarriers with therapeutic capacity for tumor targeting and penetration. |
URI: | http://dx.doi.org/10.1021/acsbiomaterials.9b01226 http://hdl.handle.net/11536/153027 |
ISSN: | 2373-9878 |
DOI: | 10.1021/acsbiomaterials.9b01226 |
期刊: | ACS BIOMATERIALS SCIENCE & ENGINEERING |
Volume: | 5 |
Issue: | 10 |
起始頁: | 5453 |
結束頁: | 5469 |
顯示於類別: | 期刊論文 |