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Designed Antitumor Peptide for Targeted siRNA Delivery into Cancer Spheroids

Cirillo, Silvia; Tomeh, Mhd Anas; Wilkinson, Robert N.; Hill, Chris; Brown, Stephen; Zhao, Xiubo

Designed Antitumor Peptide for Targeted siRNA Delivery into Cancer Spheroids Thumbnail


Authors

Silvia Cirillo

Mhd Anas Tomeh

Chris Hill

Stephen Brown

Xiubo Zhao



Abstract

Antimicrobial/anticancer peptides (AMPs/ACPs) have shown promising results as new therapeutic agents in cancer thearpy. Among them, the designed amphiphilic α-helical peptide G(IIKK)3I-NH2 (G3) displayed great affinity and specificity in targeting cancer cells. Here, we report new insights on how G3 penetrates cancer cells. G3 showed high specificity to HCT-116 colon cancer cells compared to the HDFs (human neonatal primary dermal fibroblasts) control. With high concentrations of peptide, a clear cancer cell membrane disruption was observed through SEM. Gene knockdown of the endocytic pathways demonstrated that an energy-dependent endocytic pathway is required for the uptake of the peptide. In addition, G3 can protect and selectively deliver siRNAs into cancer cells and successfully modulated their gene expression. Gene delivery was also tested in 3D cancer spheroids and showed deep penetration delivery into the cancer spheroids. Finally, the in vivo toxicity of G3 was evaluated on zebrafish embryos, showing an increasing toxicity effect with concentration. However, the toxicity of the peptide was attenuated when complexed with siRNA. In addition, negligible toxicity was observed at the concentration range for efficient gene delivery. The current results demonstrate that G3 is promising as an excellent agent for cancer therapy.

Citation

Cirillo, S., Tomeh, M. A., Wilkinson, R. N., Hill, C., Brown, S., & Zhao, X. (2021). Designed Antitumor Peptide for Targeted siRNA Delivery into Cancer Spheroids. ACS Applied Materials and Interfaces, 13(42), 49713-49728. https://doi.org/10.1021/acsami.1c14761

Journal Article Type Article
Acceptance Date Sep 28, 2021
Online Publication Date Oct 18, 2021
Publication Date Oct 27, 2021
Deposit Date Nov 1, 2021
Publicly Available Date Mar 28, 2024
Journal ACS Applied Materials and Interfaces
Print ISSN 1944-8244
Electronic ISSN 1944-8252
Publisher American Chemical Society (ACS)
Peer Reviewed Peer Reviewed
Volume 13
Issue 42
Pages 49713-49728
DOI https://doi.org/10.1021/acsami.1c14761
Keywords General Materials Science
Public URL https://nottingham-repository.worktribe.com/output/6605946
Publisher URL https://pubs.acs.org/doi/10.1021/acsami.1c14761

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