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Journal of Drug Delivery
Volume 2013 (2013), Article ID 637976, 17 pages
Review Article

Bisphosphonates and Cancer: What Opportunities from Nanotechnology?

1Department of Pharmacy, Università degli Studi di Napoli Federico II, Via Domenico Montesano 49, 8013 Naples, Italy
2Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Via Costantinopoli 16, 80138 Naples, Italy

Received 4 December 2012; Accepted 22 January 2013

Academic Editor: Stefano Salmaso

Copyright © 2013 Giuseppe De Rosa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Bisphosphonates (BPs) are synthetic analogues of naturally occurring pyrophosphate compounds. They are used in clinical practice to inhibit bone resorption in bone metastases, osteoporosis, and Paget's disease. BPs induce apoptosis because they can be metabolically incorporated into nonhydrolyzable analogues of adenosine triphosphate. In addition, the nitrogen-containing BPs (N-BPs), second-generation BPs, act by inhibiting farnesyl diphosphate (FPP) synthase, a key enzyme of the mevalonate pathway. These molecules are able to induce apoptosis of a number of cancer cells in vitro. Moreover, antiangiogenic effect of BPs has also been reported. However, despite these promising properties, BPs rapidly accumulate into the bone, thus hampering their use to treat extraskeletal tumors. Nanotechnologies can represent an opportunity to limit BP accumulation into the bone, thus increasing drug level in extraskeletal sites of the body. Thus, nanocarriers encapsulating BPs can be used to target macrophages, to reduce angiogenesis, and to directly kill cancer cell. Moreover, nanocarriers can be conjugated with BPs to specifically deliver anticancer agent to bone tumors. This paper describes, in the first part, the state-of-art on the BPs, and, in the following part, the main studies in which nanotechnologies have been proposed to investigate new indications for BPs in cancer therapy.