Multi-stimuli responsive Cu-MOFs@Keratin drug delivery system for chemodynamic therapy

Jinsong Du; Guanping Chen; Xinyi Yuan; Jiang Yuan; Li Li

doi:10.3389/fbioe.2023.1125348

Multi-stimuli responsive Cu-MOFs@Keratin drug delivery system for chemodynamic therapy

Front Bioeng Biotechnol. 2023 Feb 2:11:1125348. doi: 10.3389/fbioe.2023.1125348. eCollection 2023.

Authors

Jinsong Du^{1

2}, Guanping Chen³, Xinyi Yuan¹, Jiang Yuan², Li Li^{1

4}

Affiliations

¹ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences and the Affiliated Hospital, Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Hangzhou Normal University, Hangzhou, China.
² Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China.
³ Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China.
⁴ School of Clinical Medicine and The Affiliated Hospital, Hangzhou Normal University, Hangzhou, China.

Abstract

Although the potential of metal-organic framework (MOF) nanoparticles as drug delivery systems (DDS) for cancer treatment has been established by numerous studies, their clinical applications are still limited due to relatively poor biocompatibility. We fabricated a multifunctional Cu-MOFs@Keratin DDS for loaded drug and chemodynamic therapy (CDT) against tumor cells. The Cu-MOFs core was prepared using a hydrothermal method, and then loaded with the anticancer drug DOX and wrapped in human hair keratin. The Cu-MOFs@Keratin was well characterized by transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS). Characterization and pharmacokinetic studies of Cu-MOFs@Keratin were performed in vitro and in vivo. The keratin shell reduced the cytotoxicity and potential leakage of Cu-MOFs to normal cells, and allowed the drug-loaded nanoparticles to accumulate in the tumor tissues through enhanced permeability and retention effect (EPR). The particles entered the tumor cells via endocytosis and disintegrated under the stimulation of intracellular environment, thereby releasing DOX in a controlled manner. In addition, the Cu-MOFs produced hydroxyl radicals (·OH) by consuming presence of high intracellular levels of glutathione (GSH) and H₂O₂, which decreased the viability of the tumor cells.

Keywords: MOFs; chemodynamic therapy; drug delivery system; keratin; stimuli-responsive.

Grants and funding

This work was supported by grants from the Jiangsu Higher Education Institutions (19KJA310001 and PAPD) to JY, “Pioneer” and “Leading Goose” R&D Program of Zhejiang (Grant No. 2022C03138) and Key medical disciplines of Hangzhou to LL, and Zhejiang Province Public Welfare Technology Application Research Project (No. LTGD23C040004) to GC.