Mixed Lanthanide Oxide Nanoparticles Coated with Alginate-Polydopamine as Multifunctional Nanovehicles for Dual Modality: Targeted Imaging and Chemotherapy

Kefyalew Dagnew Addisu; Wei-Hsin Hsu; Balkew Zewge Hailemeskel; Abegaz Tizazu Andrgie; Hsiao-Ying Chou; Chiou-Hwa Yuh; Juin-Yih Lai; Hsieh-Chih Tsai

doi:10.1021/acsbiomaterials.9b01226

Mixed Lanthanide Oxide Nanoparticles Coated with Alginate-Polydopamine as Multifunctional Nanovehicles for Dual Modality: Targeted Imaging and Chemotherapy

ACS Biomater Sci Eng. 2019 Oct 14;5(10):5453-5469. doi: 10.1021/acsbiomaterials.9b01226. Epub 2019 Sep 20.

Authors

Kefyalew Dagnew Addisu¹, Wei-Hsin Hsu, Balkew Zewge Hailemeskel, Abegaz Tizazu Andrgie, Hsiao-Ying Chou, Chiou-Hwa Yuh^{2

3

4}, Juin-Yih Lai⁵, Hsieh-Chih Tsai

Affiliations

¹ Faculty of Chemical and Food Engineering, Institute of Technology, Bahir Dar University, Bahir Dar, Ethiopia P. O. Box 26.
² Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, 350 Miaoli, Taiwan.
³ Institute of Bioinformatics and Structural Biology, National Tsing Hua University, No. 101 Section 2, Guangfu Road, Hsinchu 300, Taiwan.
⁴ Department of Biological Science and Technology, National Chiao Tung University, No. 1001 Daxue Road, East District, Hsinchu 30010, Taiwan.
⁵ R&D Center for Membrane Technology, Chung Yuan Christian University, No. 200, Zhongli District, Taoyuan 320, Taiwan.

PMID: 33464065
DOI: 10.1021/acsbiomaterials.9b01226

Abstract

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 nanoparticles (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@AlgPDA 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.

Keywords: Lanthanide; Polydopamine; Spheroids; Theranostic; Tumor penetration; Zebrafish.