Enhancing tumor penetration: GSH-sensitive paclitaxel liposomes modified with Dermaseptin-PP

The dense structure of solid tumor tissues and the selective permeability of cell membranes impede the effective penetration of chemotherapeutic agent-loaded liposomes into tumors and their subsequent uptake by cells. Dermaseptin-PP, a cationic antimicrobial peptide, has demonstrated the ability to...

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Bibliographic Details
Main Authors: Ziyi Dong, Qin Zhang, Qing Zhang, Wenjun Hu, Liwen Yan, Fengqi Peng, Zucheng Hu, Jakkree Tangthianchaichana, Yueying Zhao, Shouying Du, Yang Lu
Format: Article
Language:English
Published: Elsevier 2024-10-01
Series:Materials & Design
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Online Access:http://www.sciencedirect.com/science/article/pii/S0264127524006981
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Summary:The dense structure of solid tumor tissues and the selective permeability of cell membranes impede the effective penetration of chemotherapeutic agent-loaded liposomes into tumors and their subsequent uptake by cells. Dermaseptin-PP, a cationic antimicrobial peptide, has demonstrated the ability to enhance the penetration and accumulation of drugs within solid tumors due to its unique membrane-breaking action. Based on this, we designed glutathione (GSH)-sensitive paclitaxel liposomes modified with Dermaseptin-PP. Dermaseptin-PP was modified through disulfide bonding, which could be broken at the tumor site due to high GSH levels. This cleavage resulted in the release of Dermaseptin-PP, thereby enhancing the permeability of the paclitaxel liposomes within the tumor. We found that the paclitaxel liposomes modified with Dermaseptin-PP were extensively distributed to the tumor site, and the Dermaseptin-PP modification significantly enhanced liposome penetration within the tumor. Our study significantly increased the anti-tumor efficacy of paclitaxel liposomes. Our study confirms that paclitaxel liposomes modified with Dermaseptin-PP is an effective anti-tumor therapy that enhances deep penetration into tumors. Additionally, this broadens the applications of cationic antimicrobial peptides.
ISSN:0264-1275