1. A programmable polymer library that enables the construction of stimuli-responsive nanocarriers containing logic gates.
- Author
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Zhang P, Gao D, An K, Shen Q, Wang C, Zhang Y, Pan X, Chen X, Lyv Y, Cui C, Liang T, Duan X, Liu J, Yang T, Hu X, Zhu JJ, Xu F, and Tan W
- Subjects
- Anilides chemistry, Anilides pharmacology, Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Cell Line, Tumor, Cisplatin chemistry, Cisplatin pharmacology, Drug Carriers chemical synthesis, Drug Carriers metabolism, Drug Liberation, Female, Glutathione metabolism, Humans, Hydrogen Peroxide metabolism, Logic, Mice, Nude, Nanoparticles metabolism, Polyethylene Glycols chemical synthesis, Polyethylene Glycols metabolism, Polyethyleneimine chemical synthesis, Polyethyleneimine metabolism, Proof of Concept Study, Pyridines chemistry, Pyridines pharmacology, RNA, Small Interfering chemistry, RNA, Small Interfering pharmacology, Xenograft Model Antitumor Assays, Drug Carriers chemistry, Nanoparticles chemistry, Polyethylene Glycols chemistry, Polyethyleneimine chemistry
- Abstract
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.
- Published
- 2020
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