The problem

Anabolism is the synthesis of complex molecules, and it relies on the adequate supply of energy and reducing agents. In many diseases, cells lack the energy and reducing agents they need, and therefore there is insufficient anabolism1. Molecules of ATP serve as the currency for transferring energy in cells, and they are the dominant energy source for many biological processes2. The molecule NADPH is a key reducing agent in all organisms and in many anabolic reactions3. Current medical interventions to restore anabolism in certain diseases aim to reinstate the supply of these molecules. However, a central challenge is to provide these substances to diseased cells at the correct concentration, in a controllable way.

The solution

In plants, ATP and NADPH are generated during photosynthesis: a series of reactions in which sunlight is used to produce complex, carbon-containing compounds. The reactions that produce these molecules take place in sacs known as thylakoids inside plant-cell organelles called chloroplasts. We developed nanoscale thylakoid structures, called nanothylakoid units (NTUs), with the aim of delivering them into animal cells to enhance the supply of ATP and NADPH in a light-controlled way. A big obstacle to the transfer of material between species is the recipient’s immune-mediated elimination of transplanted material. The outer membrane of cells enables mutual cellular recognition, thus preventing the immune system from eliminating the cells’ contents4. We encapsulated NTUs in cell membranes from various types of broken-down cell, including from mature chondrocytes (which make the cartilage material in joints), to camouflage the units from the immune system.

We used various cell-culture models to demonstrate the ability of the NTUs to enter cells and, when exposed to light, to boost the production of ATP and NADPH in the host cells (Fig. 1). The NTUs coated in chondrocyte membrane (CM-NTUs) could enter chondrocytes through fusion of their membrane and that of the target cell. They were able to avoid degradation by cellular organelles called lysosomes and could rapidly penetrate tissues through transcellular transport. This strategy was also verified in various other cell types in culture, including muscle satellite cells, nucleus pulposus cells and human umbilical vein endothelial cells. The NTUs also improved cell anabolism by reprogramming the metabolism of host cells. We also delivered CM-NTUs into the knee joints of mice in a model of osteoarthritis (a degenerative joint disease), and irradiated the joint with light. This approach increased ATP and NADPH availability in the treated joints, and slowed cartilage degeneration.

Future directions

Our results suggest that light-controlled NTUs derived from plants can be used to supply animal cells with ATP and NADPH, with potential therapeutic benefit. We hope to conduct early-stage clinical trials in the future to test the effects of NTUs in degenerative diseases.

In our study, both of the key photosynthetic proteins (D1 and D2) in NTUs in chondrocytes were completely degraded under illumination after about 8–16 hours. In further studies, we wish to investigate how to prolong the half-life of this photosynthetic apparatus in cells. Subsequent developments of this approach will focus on achieving optimal photosynthesis while avoiding cellular damage caused by the formation of highly reactive molecules — reactive oxygen species — under excess light.

In addition to medical applications, this photosynthetic system could also be applied to influence metabolism in cells that produce biofuels and other useful chemicals. Using nanotechnology based on the photosynthetic system to enhance the metabolism of cells might increase biofuel production while lowering costs. This could reduce the need for fossil fuels and therefore reduce carbon dioxide emissions and other greenhouse gases that contribute to climate change. Furthermore, this technology could also be used to build chemical-synthesis platforms; for example, it could be used to produce chemical reagents from renewable and carbon-neutral resources. — Pengfei Chen and Xianfeng Lin are at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.