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Bortezomib (BTZ) is mainly used to treat hematologic tumors, such as multiple myeloma and small cell lymphoma. However, its usefulness for solid tumor therapy is limited owing to its poor stability and toxicity in vivo. In the present study, an amphiphilic PEGylated dendrimer with dopamine molecule is synthesized from azide group-functionalized polyethylene glycol and alkyne group-functionalized dendrimer, which is produced from 1,1-dimethylolpropionic acid and dopamine. The amphiphilic PEGylated dendrimer with dopamine molecule reacts with BTZ to construct a BTZ prodrug-based nanoparticle through a ultrasonic emulsification method. The BTZ prodrug-based nanoparticles have greater serum stability than BTZ alone and release the prototype drug in acidic environments. The BTZ prodrug-based nanoparticle is more effective against subcutaneous tumors than BTZ itself. Furthermore, c(RGDyK) modification significantly improves the antitumor efficacy of the BTZ prodrugbased nanoparticle with regard to subcutaneous and intracranial tumors. Moreover, the BTZ prodrug-based nanoparticle significantly reduces the toxicity of BTZ in vivo. Therefore, the PEGylated BTZ dendrimer prodrug-based nanoparticles have great potential for the treatment of solid tumors in vivo.

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