Repurposing amino-bisphosphonates by liposome formulation for a new role in cancer treatment

Publication date: Available online 23 December 2019Source: Seminars in Cancer BiologyAuthor(s): Ninh M. La-Beck, Xinli Liu, Hilary Shmeeda, Claire Shudde, Alberto A. GabizonAbstractAmino-bisphosphonates (N-BPs) have been commercially available for over four decades and are used for the treatment of osteoporosis, Paget’s disease, hypercalcemia of malignancy, and bone metastases derived from various cancer types. Zoledronate and alendronate, two of the most potent N-BPs, have demonstrated direct tumoricidal activity on tumor cells and immune modulatory effects on myeloid cells and T cells in vitro and in animal models of cancer. However, the rapid renal clearance and sequestration in mineral bone of these drugs in free form severely limit their systemic exposure and applications in cancer patients. Reformulation of N-BPs by encapsulation in liposomal nanoparticles addresses these pharmacokinetic barriers, and liposomal zoledronate and alendronate formulations have been found to increase the anticancer efficacy of cytotoxic chemotherapies and adoptive T cell immunotherapies in murine cancer models. Herein, we review the differences in pharmacology between N-BPs versus non-N-BPs (e.g., clodronate), free versus liposomal N-BP formulations, and targeted versus non-targeted liposomal N-BPs, and the clinical and preclinical evidence supporting a role for liposomal N-BPs in the treatment cancer. We propose that pegylated liposomal alendronate (PLA) has the most potential for clinica...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research