In vivo phage display can identify tumor-homing proteins that are specific to the vasculature of a specific tumor tissue and the tumor vasculature is a suitable target for cancer therapy. However, such tumor-homing proteins cannot destruct tumors directly without being conjugated with anti-cancer agents. On the other hand, nanomaterials such as gold nanorods (AuNRs) can rapidly convert tissue-penetrating near infrared (NIR) irradiation into heat to raise the local temperature and thermally destruct tumors. However, AuNRs lack biological recognitions that can allow them to target and attack tumors specifically. This project is innovative because it integrates the tumor-homing proteins established by in vivo phage display and tumor-destructing AuNRs. The objectives of this application are (1) to mimic how proteins and DNA are assembled into a nanorod-like phage particle to assemble target-specific phage coat proteins and a DNA-immobilized AuNR into a phage-mimetic nanorod (PMNR) which can serve as a nano-tumor-heater and (2) to impart the breast tumor-homing specificity to the PMNR through genetically identifying tumor-homing phage coat proteins by using in vivo major coat phage display technology. The overall hypotheses of this project are that (1) major coat protein (pVIII) of nanorod-like fd-tet phage, which is genetically engineered to home to breast tumor through major coat phage display technology, can biomimetically self-assemble on the DNA-immobilized gold nanorods (AuNRs) with tumor-homing peptide motif protruding from the surface and (2) the resultant multi-functional PMNR will serve as a breast tumor-targeting nano-heater to selectively destruct breast tumor upon NIR irradiation. Three specific aims are designed to test our central hypotheses: Aim 1: Identify tumor-homing peptides that are fused to pVIII of nanorod-like phage from a phage-displayed random peptide library. Aim 2: Establish the biomimetic assembly of tumor-homing phage proteins on the DNA-immobilized AuNRs to form tumor-homing PMNRs by mimicking how pVIII is assembled along DNA during natural phage assembly. Aim 3: Test the targeted photothermal ablation of breast tumors using the tumor-targeting PMNRs. This project will result in a new tumor-homing anti-cancer agent and a novel strategy for targeted breast cancer therapy. It will also generate a novel biomimetic strategy for imparting biological recognitions to nanomaterials in nanomedicine.

PUBLIC HEALTH RELEVANCE: Phage-mimetic nanorods for targeted breast cancer treatment Project Narrative This project will use a biomimetic strategy to bring together tumor-homing proteins and tumor-destructing nanomaterials to develop a new anti-cancer agent. The new therapeutic agent can recognize breast tumors and destruct the tumors in response to a tissue-penetrating light. It will result in a novel nanotechnological strategy for targeted breast cancer therapy.

R21EB009909

2009-09-01

2012-08-31