Anticancer trail-targeted plant virus particles
An agent is described that includes a plant virus particle or VLP conjugate to TRAIL. Associating TRAIL with the plant virus particle or VLP serves to both target cancer cells and induce their apoptosis. The agent can therefore be used for a method of treating cancer in a subject.
1. An agent comprising a potato virus X (PVX) plant virus particle or virus-like particle (VLP) non-covalently conjugated to at least one tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by a non-covalent bond selected from coordination bonds between nickel-coordinated nitrilotriacetic acid (Ni-NTA) modules displayed on the PVX plant virus particle or VLP outer surface and a histidine-tag on TRAIL.
2. The agent of claim 1 , wherein the PVX plant virus particle or VLP is further loaded with or conjugated to one or more of an imaging agent, an anticancer agent, or a targeting agent.
3. The agent of claim 2 , wherein the targeting agent is an additional ligand for a tumor-associated receptor.
4. The agent of claim 3 , wherein the additional ligand is an epidermal growth factor receptor (EGFR) ligand.
5. The agent of claim 1 , wherein the PVX plant virus particle or VLP is PEGylated.
6. The agent of claim 2 , wherein the anticancer agent is a platinum-based anticancer agent.
7. The agent of claim 6 , wherein the platinum-based anticancer agent is phenanthriplatin.
8. The agent of claim 2 , wherein the anticancer agent is doxorubicin.
9. The agent of claim 2 , wherein the imaging agent is a fluorescent molecule for fluorescent imaging.
10. The agent of claim 1 , wherein TRAIL is bound to the PVX plant virus particle or VLP via N-terminus region of the ligand, providing display of C-terminus region for binding with death receptors on cancer cells.
11. The agent of claim 1 , wherein at least 100 TRAIL ligands are conjugated to the PVX plant virus particle or VLP.
12. The agent of claim 1 , wherein TRAIL comprises trimers of TRAIL monomers.