Figure 5.

Dendrimeric nanoparticles functionalized with MMP-2 activatable CPPs permitted the targeted tumor delivery of Cy5 fluorophore and MR contrast agent, gadolinium. The dual imaging properties of these particles permitted surgical planning with MRI, real-time fluorescence imaging for intraoperative assistance of tumor resection, and post-operative evaluation with MRI. Accumulation of nanoparticles provided MR contrast to identify a fibrosarcoma xenograft tumor (arrow - A). Intraoperative visualization of the tumor was achieved with fluorescence imaging prior to resection (B). Post-operative MRI revealed residual tumor tissue (box – C) whose cancerous character was confirmed with histology following removal with a second surgery (D). Similar surgical assistance was provided for melanoma xenografts. The tumor was identified with MRI (arrow – E) and fluorescence provided intraoperative visualization (F). Surgical resection was performed such that no visible fluorescence remained at the surgical site (G) and post-operative MRI confirmed the successful removal of all cancer cells (H). Tumor resection assistance with guidance by activatable CPP-nanoparticles accumulated in tumor tissue lead to prolonged tumor-free survival after removal of murine melanoma and mammary adenocarcinoma tumors. Reprinted with permission from Ref 77.