Precise localization and visualization of early-stage prostate cancer (PCa) is critical to improve the success of focal ablation and reduce cancer mortality. However, it remains challenging under the current imaging techniques due to the heterogeneous nature of PCa and the suboptimal sensitivity of the techniques themselves. Herein, a novel genetic amplified nanoparticle tumor-homing strategy to enhance the MRI accuracy of ultrasmall PCa lesions is reported. This strategy could specifically drive TfR expressions in PCa under PCa-specific DD3 promoter, and thus remarkably increase Tf-USPIONs concentrations in a highly accurate manner while minimizing their non-specific off-target effects on normal tissues. Consequently, this strategy can pinpoint an ultrasmall PCa lesion, which is otherwise blurred in the current MRI, and thereby addresses the unmet key need in MRI imaging for focal therapy. With this proof-of-concept experiment, the synergistic gene-nano strategy holds great promise to boost the MRI effects of a wide variety of commonly used nanoscale and molecular probes that are otherwise limited. In addition, such a strategy may also be translated and applied to MR-specific imaging of other types of cancers by using their respective tumor-specific promoters.

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