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Regulation of cellular oxidative stress plays a critical role in revealing the molecular mechanisms of cellular activities and thus is a potential strategy for tumor treatment. Optical methods have been employed for intelligent regulation of oxidative stress in tumor regions. However, long‐time continuous irradiation inevitably causes damage to normal tissues. Herein, a ferrocene‐containing nucleic acid‐based energy‐storage nanoagent was designed to achieve the continuous photo‐regulation of cellular oxidative stress in the dark. Specifically, the photoenergy stored in the agent could convert effectively and accelerate Fenton‐like reaction continuously, augmenting cellular oxidative stress. This nanoagent could also silence oxidative damage repair genes to further amplify oxidative stress. This strategy not only provides oxidative stress regulation for studying the molecular mechanisms of biological activities, but also offers a promising step toward tumor microenvironment modulation. [ABSTRACT FROM AUTHOR]

Regulation of protein activity is essential for revealing the molecular mechanisms of biological processes. DNA and RNA achieve many uniquely efficient functions, such as genetic expression and regulation. The chemical capability to synthesize artificial nucleotides can expand the chemical space of nucleic acid libraries and further increase the functional diversity of nucleic acids. Herein, a versatile method has been developed for modular expansion of the chemical space of nucleic acid libraries, thus enabling the generation of aptamers able to regulate protein activity. Specifically, an aptamer that targets integrin alpha3 was identified and this aptamer can inhibit cell adhesion and migration. Overall, this chemical‐design‐assisted in vitro selection approach enables the generation of functional nucleic acids for elucidating the molecular basis of biological activities and uncovering a novel basis for the rational design of new protein‐inhibitor pharmaceuticals. Artificial‐nucleotide aptamer: The chemical‐design‐assisted in vitro selection approach reported enables the generation of a new class of functional nucleic acids for regulating the biologically relevant performance of its target molecule. This uncovers a novel basis for the rational design of new protein‐inhibitor pharmaceuticals. [ABSTRACT FROM AUTHOR]