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Traditional targeting nanoprobes suffer from the risks of partial loss of targeting activity and nanoparticle aggregation induced by post-synthetic modifications, ambiguous toxicity, tedious synthesis procedures and environmentally hazardous processes. Herein, we report a green and facile strategy to fabricate transferrin–indocyanine green nanoparticles as a smart theranostic agent with intrinsic biosafety and active targeting abilities for near-infrared fluorescent imaging and photothermal therapy of tumors. Simple mixing of transferrin and indocyanine green enables their self-assembly in aqueous solution to form nanoparticles with excellent water solubility, colloidal stability, favorable biocompatibility and impressive active targeting theranostic effects in vitro and in vivo. The transferrin–indocyanine green nanoparticles show great potential in theranostic applications of tumors in clinical therapy.

Graphical abstract: Green and facile synthesis of a theranostic nanoprobe with intrinsic biosafety and targeting abilities

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