Figure 4.

Examples of PNP-mediated delivery of biotherapeutics and imaging agents. (Upper panel) TRAIL-based therapy: PVX-mediated delivery of the anti-cancer biotherapeutic HisTRAIL. (A) Schematic showing PVX–HisTRAIL-induced apoptosis via caspase dependent pathway. (B) IC₅₀ of free His-TRAIL and PVX–HisTRAIL against various cancer cell types (C). PVX–HisTRAIL activated caspase 8 and caspase 3/7. (D,E) In comparison to free HisTRAIL, PVX–HisTRAIL significantly regressed tumor growth in tumor-bearing mice after 30 days. Adapted from [24], with permission from American Chemical Society, 2019. (Lower Panel) Magnetic resonance imaging (MRI): Hsp-mediated delivery of the MRI contrast agent Gd–DTPA. (F) Design of Hsp variants for Gd–DTPA delivery. (G) Hsp was modified with a C-terminal iRGD to target pancreatic cancer cells. To generate variants of different sizes, hydrophobic peptides repeats were attached at the N-terminus of Hsp, resulting in: 1-nanocage, 2-nanocage, 3-nanocage, and 4-nanocage. (H) Relaxivity values (at 1.5 Tesla) for each iRGD–Hsp variant of free Gd–DTPA, in vitro. (I,J) In vivo MRI images (9.4 T) in transgenic mice bearing pancreatic tumors 6h after IV injection. The ‘4-nanocage’ variant showed a significantly higher tumor-to-normal MRI contrast ratio than free Gd–DTPA. Adapted from [38], with permission from Elsevier, 2018.