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Following these guidelines, NPs can be designed to target and treat diseases more efficiently than small molecules, have minimum accumulation in normal tissues, and induce minimum toxicity. In this Minireview, we integrate this guidance with our ten\u2010year studies on developing renal clearable luminescent gold NPs. These gold NPs resist serum protein adsorption, escape liver uptake, target cancerous tissues, and report kidney dysfunction at early stages. At the same time, off\u2010target gold NPs can be eliminated by the kidneys with minimum accumulation in the body. 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