A programmable polymer library that enables the construction of stimuli-responsive nanocarriers containing logic gates

• Published in: Nature chemistry 2020-04, Vol.12 (4), p.381-390
• Main Authors: Zhang, Penghui, Gao, Di, An, Keli, Shen, Qi, Wang, Chen, Zhang, Yuchao, Pan, Xiaoshu, Chen, Xigao, Lyv, Yifan, Cui, Cheng, Liang, Tingxizi, Duan, Xiaoman, Liu, Jie, Yang, Tielin, Hu, Xiaoxiao, Zhu, Jun-Jie, Xu, Feng, Tan, Weihong
• Format: Article
• Language: English
• Subjects: 631/1647/350/354; 639/638/298/54/152; Analytical Chemistry; Anilides - chemistry; Anilides - pharmacology; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biochemistry; Biomarkers; Biomaterials; Biomedical materials; Cell Line, Tumor; Cell therapy; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Cisplatin - chemistry; Cisplatin - pharmacology; Construction; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - metabolism; Drug delivery systems; Drug Liberation; Female; Gates; Glutathione - metabolism; Humans; Hydrogen Peroxide - metabolism; Inorganic Chemistry; Kinases; Libraries; Logic; Logic circuits; Mice, Nude; Nanoparticles - chemistry; Nanoparticles - metabolism; Nanotechnology devices; Organic Chemistry; Physical Chemistry; Plug & play; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polyethylene Glycols - metabolism; Polyethyleneimine - chemical synthesis; Polyethyleneimine - chemistry; Polyethyleneimine - metabolism; Polymers; Precision medicine; Proof of Concept Study; Pyridines - chemistry; Pyridines - pharmacology; Ribonucleic acid; RNA; RNA, Small Interfering - chemistry; RNA, Small Interfering - pharmacology; siRNA; Stem cells; Stimuli; Structural hierarchy; Tissue engineering; Xenograft Model Antitumor Assays
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/s41557-020-0426-3

Stimuli-responsive biomaterials that contain logic gates hold great potential for detecting and responding to pathological markers as part of clinical therapies. However, a major barrier is the lack of a generalized system that can be used to easily assemble different ligand-responsive units to form programmable nanodevices for advanced biocomputation. Here we develop a programmable polymer library by including responsive units in building blocks with similar structure and reactivity. Using these polymers, we have developed a series of smart nanocarriers with hierarchical structures containing logic gates linked to self-immolative motifs. Designed with disease biomarkers as inputs, our logic devices showed site-specific release of multiple therapeutics (including kinase inhibitors, drugs and short interfering RNA) in vitro and in vivo. We expect that this ‘plug and play’ platform will be expanded towards smart biomaterial engineering for therapeutic delivery, precision medicine, tissue engineering and stem cell therapy. A programmable polymer library that responds to external and internal stimuli has been developed and used to fabricate a series of nanocarriers for drug release. The carriers respond to disease biomarkers, triggering self-immolative motifs and leading to the site-specific release of therapeutics both in vitro and in vivo.