Probes, methods of making probes, and methods of use

A method of imaging a brain tumor, comprising the steps of:

• (a) delivering to a subject human or animal a composition comprising a multimodal nanoprobe, said multimodal nanoprobe comprising a nanoparticle core, a reporter compound layer disposed on the core, a silica shell consisting of polymeric silicon dioxide linking 3-mercaptopropyl-trimethoxysilane (MPTMS) moieties directly attached to the nanoparticle core surrounding the reporter compound layer and the core, and a plurality of MRI-detectable agents disposed on the silica shell;
• wherein the core is a photoacoustic probe having a detectable photoacoustic signal;
• wherein the reporter compound is a Raman-active reporter, wherein the interaction of the Raman-active reporter with the core produces a detectable vibrational signal;
• (b) preoperatively obtaining a MRI signal from the multimodal nanoprobe in the tumorous tissue within the brain of the subject human or animal and generating from the MRI signal a first image, wherein the first image indicates a location of tumorous brain tissue and a macroscopic delineation thereof within the brain of the subject human or animal;
• (c) intra-operatively obtaining a deep tissue penetration photoacoustic signal from the multimodal nanoprobe in the tumorous tissue within the brain of the subject human or animal and generating from the photoacoustic signal a second image, wherein the second image indicates the location of tumorous brain tissue within the brain of the subject human or animal;
• (d) intra-operatively obtaining a Raman vibrational signal from the multimodal nanoprobe in the tumorous tissue within the brain of the subject human or animal and generating from the Raman vibrational signal a third image, wherein the third image indicates the margin of tumorous brain tissue within the brain of the subject human or animal;
• and
• (e) intra-operatively overlaying at least two of the first, the second, and the third images with an MR image of the brain of the subject human or animal to generate an overlay image of the tumorous brain tissue within the brain of the subject human or animal by and determining from said overlay image at least one of the location and the margin of the tumorous brain tissue within the brain of the subject human or animal.