Intracellular Delivery of Therapeutic Protein via Ultrathin Layered Double Hydroxide Nanosheets

He Zhang; Anle Ge; Yulin Wang; Boran Xia; Xichu Wang; Zhonghui Zheng; Changsheng Wei; Bo Ma; Lin Zhu; Rose Amal; Sung Lai Jimmy Yun; Zi Gu

doi:10.3390/pharmaceutics16030422

Pharmaceutics (Mar 2024)

Intracellular Delivery of Therapeutic Protein via Ultrathin Layered Double Hydroxide Nanosheets

He Zhang,
Anle Ge,
Yulin Wang,
Boran Xia,
Xichu Wang,
Zhonghui Zheng,
Changsheng Wei,
Bo Ma,
Lin Zhu,
Rose Amal,
Sung Lai Jimmy Yun,
Zi Gu

Affiliations

He Zhang: School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
Anle Ge: Single-Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics, Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China
Yulin Wang: School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
Boran Xia: School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
Xichu Wang: School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
Zhonghui Zheng: Shandong Xinhua Pharmaceutical Co., Ltd., Zibo 255086, China
Changsheng Wei: Shandong Xinhua Pharmaceutical Co., Ltd., Zibo 255086, China
Bo Ma: Single-Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics, Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China
Lin Zhu: Australian Carbon Materials Centre (A-CMC), School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
Rose Amal: School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
Sung Lai Jimmy Yun: College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China
Zi Gu: School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia

DOI: https://doi.org/10.3390/pharmaceutics16030422
Journal volume & issue: Vol. 16, no. 3
p. 422

Abstract

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The therapeutic application of biofunctional proteins relies on their intracellular delivery, which is hindered by poor cellular uptake and transport from endosomes to cytoplasm. Herein, we constructed a two-dimensional (2D) ultrathin layered double hydroxide (LDH) nanosheet for the intracellular delivery of a cell-impermeable protein, gelonin, towards efficient and specific cancer treatment. The LDH nanosheet was synthesized via a facile method without using exfoliation agents and showed a high loading capacity of proteins (up to 182%). Using 2D and 3D 4T1 breast cancer cell models, LDH–gelonin demonstrated significantly higher cellular uptake efficiency, favorable endosome escape ability, and deep tumor penetration performance, leading to a higher anticancer efficiency, in comparison to free gelonin. This work provides a promising strategy and a generalized nanoplatform to efficiently deliver biofunctional proteins to unlock their therapeutic potential for cancer treatment.

Published in Pharmaceutics

ISSN: 1999-4923 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica
Website: http://www.mdpi.com/journal/pharmaceutics/

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