Peptide-functionalised magnetic silk nanoparticles produced by a swirl mixer for enhanced anticancer activity of ASC-J9

Mhd Anas Tomeh; Roja Hadianamrei; Defeng Xu; Stephen Brown; Xiubo Zhao

doi:10.1016/j.colsurfb.2022.112549

Peptide-functionalised magnetic silk nanoparticles produced by a swirl mixer for enhanced anticancer activity of ASC-J9

Colloids Surf B Biointerfaces. 2022 Aug:216:112549. doi: 10.1016/j.colsurfb.2022.112549. Epub 2022 May 10.

Authors

Mhd Anas Tomeh¹, Roja Hadianamrei¹, Defeng Xu², Stephen Brown³, Xiubo Zhao⁴

Affiliations

¹ Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S1 3JD, UK.
² School of Pharmacy, Changzhou University, Changzhou 213164, China.
³ Department of Biomedical Science, University of Sheffield, Sheffield S1 2TN, UK.
⁴ Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S1 3JD, UK; School of Pharmacy, Changzhou University, Changzhou 213164, China. Electronic address: xiubo.zhao@cczu.edu.cn.

PMID: 35636321
DOI: 10.1016/j.colsurfb.2022.112549

Abstract

Silk fibroin is an FDA approved biopolymer for clinical applications with great potential in nanomedicine. However, silk-based nanoformulations are still facing several challenges in processing and drug delivery efficiency (such as reproducibility and targetability), especially in cancer therapy. To address these challenges, robust and controllable production methods are required for generating nanocarriers with desired properties. This study aimed to develop a novel method for the production of peptide-functionalized magnetic silk nanoparticles with higher selectivity for cancer cells for targeted delivery of the hydrophobic anticancer agent ASC-J9. A new microfluidic device with a swirl mixer was designed to fabricate magnetic silk nanoparticles (MSNP) with desired size and narrow size distribution. The surface of MSNPs was functionalized with a cationic amphiphilic anticancer peptide, G(IIKK)₃I-NH₂ (G3), to enhance their selectivity towards cancer cells. The G3-MSNPs increased the cellular uptake and anticancer activity of G3 in HCT 116 colorectal cancer cells compared to free G3. Moreover, the G3-MSNPs exhibited considerably higher cellular uptake and cytotoxicity in HCT 116 colorectal cancer cells compared to normal cells (HDFs). Encapsulating ASC-J9 in G3-MSNPs resulted in augmented anticancer activity compared to free ASC-J9 and non-functionalized ASC-J9 loaded MSNPs within its biological half-life. Hence, functionalizing MSNPs with G3 enabled targeted delivery of ASC-J9 to cancer cells and enhanced its anticancer effect. Functionalization of nanoparticles with anticancer peptides could be regarded as a new strategy for targeted delivery and enhanced efficiency of anticancer drugs. Furthermore, the microfluidic device introduced in this paper offers a robust and reproducible method for fabrication of small sized homogenous nanoparticles.

Keywords: Cancer therapy; Magnetic silk nanoparticles; Microfluidics; Peptide-functionalized nanoparticles; Targeted drug delivery.

MeSH terms

Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Colorectal Neoplasms*
Drug Delivery Systems
Humans
Magnetic Phenomena
Nanoparticles* / chemistry
Peptides / pharmacology
Reproducibility of Results
Silicon Dioxide / chemistry
Silk

Substances

Antineoplastic Agents
Peptides
Silk
Silicon Dioxide