Rutin-Doped Hybrid Nanoparticles: Effect of the Molecular Doping Density on T ₁ Relaxivity and Their Application in Targeted Magnetic Resonance Imaging of Malignant Tumors

Molecular doping is a promising strategy to tune the performance such as relaxivity and targeting ability of magnetic resonance imaging (MRI) nanocontrast agents. Herein, hybrid nanoparticles of amphiphilic manganese complex (MnL) and DSPE-PEG were first prepared, and it was found that a higher DSPE-PEG doping density reduced size and increased T 1 relaxivity. Then, rutin (Ru) doping further transformed hybrid nanoparticle morphology from spherical to snowflake-like, decreased size, and enhanced T 1 relaxivity by increasing the number of coordinated water molecules ( q ) and water exchange rate (1/τ M ). Ru-doped hybrid nanoparticles (MnL/Ru NP5) with a MnL/DSPE-PEG/Ru mass ratio of 1/2/4 exhibited the highest T 1 relaxivity and good stability and biosafety and were selected for in vivo tumor-targeted MRI. MnL/Ru NP5 shows promise for MRI of H22 tumors thanks to its effective glucose transporters (GLUTs)-mediated tumor-cell-targeting ability. Our molecular doping strategy provides a potential way for the structural design of high-performance hybrid nanocontrast agents.