In this work we report the development of the tri-functionalized mesoporous silica nanoparticles (MSNs) for use as theranostic compounds that orchestrate the trio of imaging, target and therapy in a single particle. The MSNs are functionalized in sequence with (1) contrast agents that enable traceable imaging of particle targeting, (2) drug payloads for therapeutic intervention and, (3) biomolecular ligands for highly-targeted particle delivery. Traceable imaging of nanoparticles was accomplished by directly incorporating a near-infrared (NIR) fluorescent contrast agent, ATTO647N, into the silica framework of MSNs, to exploit the relative transparency of most tissues at NIR wavelengths and maximize MSN surface area available for the subsequent conjugating drugs and targeting ligands. An oxygen-sensing, palladium-porphyrin based photosensitizer (Pd-porphyrin; PdTPP) was incorporated into the MSN's nanochannels, to enable photodynamic therapy (PDT). cRGDyK peptides, tiling the outermost surfaces of MSNs, were used for targeting the overexpressed αvβ3 integrins of cancer cells, and to ensure the internalization of the photosensitizer PdTPP. In vitro cell evaluation of the theranostic platform demonstrated not only excellent targeting specificity and minimal collateral damage, but highly potent therapeutic effect as well.
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