Liposomal Drug Delivery in Cancer : Hematological Malignancies and Beyond

Abstract

In the present work, liposomes loaded with glucocorticoids or proteasome inhibitors were studied in two clinically more relevant mouse tumor models: A spontaneous MMTV/neu mouse model of breast cancer. In this model, mouse mammary tumor virus (MMTV) is used to engineer overexpression of the neuoncogene. Neu genomic amplifications are present in 20–30% of human breast cancers, also in invasive ductal carcinomas. As a result of neu overexpression, the mice develop mammary tumors after several months, showing slower and clinically more relevant tumor growth kinetics compared to many subcutaneous xenograft models and a multiple myeloma model with a reconstituted human hematopoietic niche is created in ossicles. Tumors are created by injection of either multiple myeloma cell lines or patient derived primary cells. The human bone environment is mimicked in by interaction of myeloma cells to bone marrow stromal cells. Moreover, angiogenesis is developed within and around the tumor bearing scaffolds.