Complex experimental design is a common problem in the preparation of theranostic nanoparticles, resulting in poor reaction control, expensive production cost, and low experiment success rate. The present study aims to develop PEGylated bismuth (PEG-Bi) nanoparticles with a precisely controlled one-pot approach, which contains only methoxy[(poly-(ethylene glycol)]trimethoxy-silane (PEG-silane) and bismuth oxide (Bi 2 O 3 ). A targeted pyrolysis of PEG-silane was achieved to realize its roles as both the reduction and PEGylation agents. The unwanted methoxy groups of PEG-silane were selectively pyrolyzed to form reductive agents, while the useful PEG-chain was fully preserved to enhance the biocompatibility of Bi nanoparticles. Moreover, Bi 2 O 3 not only acted as the raw material of the Bi source but also presented a self-promotion in the production of Bi nanoparticles via catalyzing the pyrolysis of PEG-silane. The reaction mechanism was systematically validated with different methods such as nuclear magnetic resonance spectroscopy. The PEG-Bi nanoparticles showed better compatibility and photothermal conversion than those prepared by the complex multiple step approaches in literature studies. In addition, the PEG-Bi nanoparticles possessed prominent performance in X-ray computed tomography imaging and photothermal cancer therapy in vivo. The present study highlights the art of precise reaction control in the synthesis of PEGylated nanoparticles for biomedical applications.
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