A plant-derived natural photosynthetic system for improving cell anabolism

Pengfei Chen, Xin Liu, Chenhui Gu, Peiyu Zhong, Nan Song, Mobai Li, Zhanqiu Dai, Xiangqian Fang, Zhaoming Liu, Jianfeng Zhang, Ruikang Tang (), Shunwu Fan () and Xianfeng Lin ()
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Pengfei Chen: Zhejiang University School of Medicine
Xin Liu: Zhejiang University School of Medicine
Chenhui Gu: Zhejiang University School of Medicine
Peiyu Zhong: Zhejiang University School of Medicine
Nan Song: Zhejiang University School of Medicine
Mobai Li: Zhejiang University School of Medicine
Zhanqiu Dai: Zhejiang University School of Medicine
Xiangqian Fang: Zhejiang University School of Medicine
Zhaoming Liu: Zhejiang University
Jianfeng Zhang: Zhejiang University School of Medicine
Ruikang Tang: Zhejiang University
Shunwu Fan: Zhejiang University School of Medicine
Xianfeng Lin: Zhejiang University School of Medicine

Nature, 2022, vol. 612, issue 7940, 546-554

Abstract: Abstract Insufficient intracellular anabolism is a crucial factor involved in many pathological processes in the body1,2. The anabolism of intracellular substances requires the consumption of sufficient intracellular energy and the production of reducing equivalents. ATP acts as an ‘energy currency’ for biological processes in cells3,4, and the reduced form of NADPH is a key electron donor that provides reducing power for anabolism5. Under pathological conditions, it is difficult to correct impaired anabolism and to increase insufficient levels of ATP and NADPH to optimum concentrations1,4,6–8. Here we develop an independent and controllable nanosized plant-derived photosynthetic system based on nanothylakoid units (NTUs). To enable cross-species applications, we use a specific mature cell membrane (the chondrocyte membrane (CM)) for camouflage encapsulation. As proof of concept, we demonstrate that these CM-NTUs enter chondrocytes through membrane fusion, avoid lysosome degradation and achieve rapid penetration. Moreover, the CM-NTUs increase intracellular ATP and NADPH levels in situ following exposure to light and improve anabolism in degenerated chondrocytes. They can also systemically correct energy imbalance and restore cellular metabolism to improve cartilage homeostasis and protect against pathological progression of osteoarthritis. Our therapeutic strategy for degenerative diseases is based on a natural photosynthetic system that can controllably enhance cell anabolism by independently providing key energy and metabolic carriers. This study also provides an enhanced understanding of the preparation and application of bioorganisms and composite biomaterials for the treatment of disease.

Date: 2022
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DOI: 10.1038/s41586-022-05499-y

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