Targeting Extracellular Matrix Glycoproteins in Metastases for Tumor-Initiating Cell Therapy

Abstract

Abstract : The proposed research is a proof-of-concept study that focuses on testing a new cancer targeting strategy that aims at enhancing nanodelivery of drugs to osteopontin (OPN) that are often overexpressed in advanced prostate cancer cells and their microenvironment. To evaluate this strategy, lipid-based nanocarrier that targets OPN (i.e. OPN-LN) was developed, characterized and compared with non-targeting LN. This OPN-LN was used as the key platform to study the OPN targeting strategy. In the reporting period, OPN-LN was prepared by conjugation of OPN antibody onto the surface of lipid nanocarriers using SATA as the conjugation reagent. Our data show that the OPN-LN have good dispersion stability (no noticeable aggregation at 37 deg C in 2 days) and regular morphology. When compared with non-targeting LN, OPN-LN were more efficiently taken up by PC-3M prostate cancer cells which were shown to be OPN expressing as indicated by Western blotting analysis. No significant increase in non-specific toxicity was observed after OPN antibody conjugation. In brief, OPN targeting apparently can improve the nanodelivery to OPN expressing prostate cancer cells. The impact on anticancer efficacy will be evaluated in the next reporting period.