Effective and Selective Anti‐Cancer Protein Delivery via All‐Functions‐in‐One Nanocarriers Coupled with Visible Light‐Responsive,Reversible Protein Engineering |
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| Authors: | Hua He Yongbing Chen Yongjuan Li Ziyuan Song Yinan Zhong Rongying Zhu Jianjun Cheng Lichen Yin |
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| Affiliation: | 1. Jiangsu Key Laboratory for Carbon‐Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Joint International Research Laboratory of Carbon‐Based Functional Materials and Devices, Soochow University, Suzhou, China;2. Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China;3. Department of Materials Science and Engineering, University of Illinois at Urbana‐Champaign, Urbana, IL, USA;4. Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, China |
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| Abstract: | Efficient intracellular delivery of protein drugs and tumor‐specific activation of protein functions are critical toward anti‐cancer protein therapy. However, an omnipotent protein delivery system that can harmonize the complicated systemic barriers as well as spatiotemporally manipulate protein function is lacking. Herein, an “all‐functions‐in‐one” nanocarrier doped with photosensitizer (PS) is developed and coupled with reactive oxygen species (ROS)‐responsive, reversible protein engineering to realize cancer‐targeted protein delivery, and spatiotemporal manipulation of protein activities using long‐wavelength visible light (635 nm) at low power density (5 mW cm?2). Particularly, RNase A is caged with H2O2‐cleavable phenylboronic acid to form 4‐nitrophenyl 4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)benzyl carbonate (NBC)‐modified RNase (RNBC), which is encapsulated in acid‐degradable, ketal‐crosslinked PEI (KPEI)‐based nanocomplexes (NCs) coated with PS‐modified hyaluronic acid (HA). Such NCs harmonize the critical processes for protein delivery, wherein HA coating renders NCs with long blood circulation and cancer cell targeting, and KPEI enables endosomal escape as well as acid‐triggered intracellular RNBC release. Tumor‐specific light irradiation generates H2O2 to kill cancer cells and restore the protein activity, thus achieving synergistic anti‐cancer efficacy. It is the first time to photomanipulate protein functions by coupling ROS‐cleavable protein caging with PS‐mediated ROS generation, and the “all‐functions‐in‐one” nanocarrier represents a promising example for the programmed anti‐cancer protein delivery. |
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| Keywords: | cancer therapy intracellular protein delivery light responsiveness protein caging ROS responsiveness |
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