Folate-Targeted Proteolytic Macromolecules for Targeted Drug Delivery and Optical Tumor Imaging

摘要

Currently available therapies for breast cancer are limited by nonspecificity and system toxicities. Nanotechnology-based approaches offer an elegant means to overcome these limitations by multiplexing functional chemistries for medical image contrast and therapy with moieties for enhanced solubility and drug delivery. The dually-targeted, multifunctional nanoparticles we are developing are designed to selectively target and effectively diagnose or treat breast tumors, limiting damage to normal tissue and reducing side effects associated with traditional cancer therapies. The findings reported herein demonstrate that we have the ability to synthesize and characterize the key components of protelytic nanobeacons (PNBs) and proteolytic nanotherapeutics (PNTs). Furthermore, we have verified enzymatic cleavability and of substrate peptides and established methods by which to assess MMP selectivity. Evidence from in vitro and in vivo experiments suggests that the proposed strategy for MMPactivated selective delivery of diagnostic and therapeutic reagents is feasible. We propose to proceed with the development of PNBs and PNTs with broadly MMP-selective substrates in parallel with screening for one appropriate for MMP14. The ultimate goal of this research is to provide a means to improve both the survival and the quality of life of people diagnosed with breast cancer.