Research Project
10290529
Abstract The treatment outcome of metastatic osteosarcoma (mOS) remains poor and has not improved for over four decades. Thus, developing novel approaches for treating mOS is urgently needed. We unexpectedly find that enzyme-instructed self-assembly (EISA) is able to form nanofibers (NFs) inside the nuclei of mOS cells and selectively killing the mOS cells in cell culture. This proposed pilot study is to test the in-situ formed NFs for inhibiting tumor growth in murine models. This research program will focus on two specific aims: Aim 1, synthesis and characterization of the molecules for EISA in the nuclei of mOS cells; Aim 2, pilot study of the EISA substrates for inhibiting mOS tumors in clinically relevant murine models. The rigor of prior research is that (i) overexpression of alkaline phosphatase (ALP) is a key feature of mOS, (ii) our preliminary results show that EISA forms NFs inside nuclei to selectively inhibit mOS cells, and (iii) EISA forms cytosolic NFs to selectively inhibit mOS tumors in vivo. The innovation is to target the nuclei of mOS cells by EISA. The success of the proposed studies will contribute to the development of new molecular targeting agents for selectively killing mOS, which may ultimately lead to breakthrough in treating mOS.
