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
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.
