L. Mirabello, R. J. Troisi, and S. A. Savage, Osteosarcoma Incidence and Survival Rates from 1973 to 2004: Data from the Surveillance, Epidemiology, and End Results Program, Cancer, vol.115, issue.7, pp.1531-1543, 2009.

, Key Statistics for Osteosarcoma, 2018.

P. C. Valery, M. Laversanne, and F. Bray, Bone Cancer Incidence by Morphological Subtype: A Global Assessment, Cancer Causes Control, vol.26, issue.8, pp.1127-1139, 2015.

M. S. Isakoff, S. S. Bielack, P. Meltzer, and R. Gorlick, Osteosarcoma: Current Treatment and a Collaborative Pathway to Success, J. Clin. Oncol, vol.33, issue.27, pp.3029-3035, 2015.

S. Ferrari and M. Serra, An Update on Chemotherapy for Osteosarcoma, Expert Opin. Pharmacother, vol.16, issue.18, pp.2727-2736, 2015.

J. K. Anninga, H. Gelderblom, M. Fiocco, J. R. Kroep, A. H. Taminiau et al., Chemotherapeutic Adjuvant Treatment for Osteosarcoma: Where Do We Stand?, Eur. J. Cancer, vol.47, issue.16, pp.2431-2445, 2011.

G. Bacci, A. Briccoli, M. Rocca, S. Ferrari, D. Donati et al., Neoadjuvant Chemotherapy for Osteosarcoma of the Extremities with Metastases at Presentation: Recent Experience at the Rizzoli Institute in 57 Patients Treated with Cisplatin, Doxorubicin, and a High Dose of Methotrexate and, Ifosfamide. Ann. Oncol, vol.14, issue.7, pp.1126-1134, 2003.

W. Kim, I. Han, J. S. Lee, H. S. Cho, J. W. Park et al., Postmetastasis Survival in High-Grade Extremity Osteosarcoma: A Retrospective Analysis of Prognostic Factors in 126 Patients, J. Surg. Oncol, vol.117, issue.6, pp.1223-1231, 2018.

J. Wu, H. Sun, J. Li, Y. Guo, K. Zhang et al., Increased Survival of Patients Aged 0?29 Years with Osteosarcoma: A Period Analysis, Cancer Med, vol.7, issue.8, pp.3652-3661, 1984.

E. Puljula, P. Turhanen, J. Vepsalaïnen, M. Monteil, M. Lecouvey et al., Structural Requirements for Bisphosphonate Binding on Hydroxyapatite: NMR Study of Bisphosphonate Partial Esters, ACS Med. Chem. Lett, vol.6, issue.4, pp.397-401, 2015.

L. E. Cole, T. Vargo-gogola, and R. K. Roeder, Targeted Delivery to Bone and Mineral Deposits Using Bisphosphonate Ligands, Adv. Drug Delivery Rev, vol.99, pp.12-27, 2016.

C. H. Van-poznak, S. Temin, G. C. Yee, N. A. Janjan, W. E. Barlow et al., of Clinical Oncology Executive Summary of the Clinical Practice Guideline Update on the Role of Bone-Modifying Agents in Metastatic Breast Cancer, J. Clin. Oncol, vol.29, issue.9, pp.1221-1227, 2011.

A. A. Yusuf, S. R. Cummings, N. B. Watts, M. T. Feudjo, J. M. Sprafka et al., Real-World Effectiveness of Osteoporosis Therapies for Fracture Reduction in Post-Menopausal Women, Arch Osteoporos, vol.13, issue.1, p.33, 2018.

M. Abdelkarim, E. Guenin, O. Sainte-catherine, N. Vintonenko, N. Peyri et al., New Symmetrically Esterified M-Bromobenzyl Non-Aminobisphosphonates Inhibited Breast Cancer Growth and Metastases, vol.4, p.4685, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00416602

E. Guenin, D. Ledoux, O. Oudar, M. Lecouvey, and M. Kraemer, Structure-Activity Relationships of a New Class of Aromatic Bisphosphonates That Inhibit Tumor Cell Proliferation In Vitro, Anticancer Res, vol.25, issue.2A, pp.1139-1145, 2005.

H. Fleisch, R. G. Russell, S. Bisaz, P. A. Casey, and R. C. Mu?lbauer, The Influence of Pyrophosphate Analogues (Diphosphonates) on the Precipitation and Dissolution, Calcif. Tissue Res, vol.2, pp.10-10, 1968.

E. Van-beek, M. Van-hoekstra, M. Van-de-ruit, C. Lo?ik, P. et al., Structural Requirements for Bisphosphonate Actions in Vitro, J. Bone Miner. Res, vol.9, issue.12, pp.1875-1882, 1994.

E. Van-beek, C. Van-lo?ik, I. Que, P. , and S. , Dissociation of Binding and Antiresorptive Properties of Hydroxybisphosphonates by Substitution of the Hydroxyl with an Amino Group, J. Bone Miner. Res, vol.11, issue.10, pp.1492-1497, 1996.

M. Egorov, Y. Fortun, D. Heymann, J. Lebreton, M. Mathe et al., Method for Synthesizing Hydroxy-Bisphosphonic Acid Derivatives, International Patent Application WO, 2009.

R. Hu, H. Zheng, J. Cao, Z. Davoudi, W. et al., Synthesis and In Vitro Characterization of Carboxymethyl Chitosan-CBA-Doxorubicin Conjugate Nanoparticles as pH-Sensitive Drug Delivery Systems, J. Biomed. Nanotechnol, vol.13, p.1097, 2017.

R. Hu, H. Zheng, J. Cao, Z. Davoudi, W. et al., Self-Assembled Hyaluronic Acid Nanoparticles for pH-Sensitive Release of Doxorubicin: Synthesis and In Vitro Characterization, J. Biomed. Nanotechnol, vol.13, p.1058, 2017.

X. Zhang, H. Zhang, L. Yin, R. Hu, T. Qiu et al., PH-Sensitive Nanosystem Based on Carboxymethyl Chitosan for Tumor-Targeted Delivery of Daunorubicin, J. Biomed. Nanotechnol, vol.12, issue.8, pp.1688-1698, 2016.

H. Zheng, L. Yin, X. Zhang, H. Zhang, R. Hu et al., Redox Sensitive Shell and Core Crosslinked Hyaluronic Acid Nanocarriers for Tumor-Targeted Drug Delivery, J. Biomed. Nanotechnol, vol.12, issue.8, pp.1641-1653, 2016.

S. Rudnick-glick, E. Corem-salkmon, I. Grinberg, R. Yehuda, and S. Margel, Near IR Fluorescent Conjugated Poly-(Ethylene Glycol)Bisphosphonate Nanoparticles for in Vivo Bone Targeting in a Young Mouse Model, J. Nanobiotechnol, vol.13, 2015.

S. Rudnick-glick, E. Corem-salkmon, I. Grinberg, and S. Margel, Targeted Drug Delivery of near IR Fluorescent Doxorubicin-Conjugated Poly(Ethylene Glycol) Bisphosphonate Nanoparticles for Diagnosis and Therapy of Primary and Metastatic Bone Cancer in a Mouse Model, J. Nanobiotechnol, vol.14, 2016.

K. B. Farrell, A. Karpeisky, D. H. Thamm, and S. Zinnen, Bisphosphonate Conjugation for Bone Specific Drug Targeting, Bone Rep, vol.9, pp.47-60, 2018.

R. N. Young and M. D. Grynpas, Targeting Therapeutics to Bone by Conjugation with Bisphosphonates, Curr. Opin. Pharmacol, vol.40, pp.87-94, 2018.

S. W. Morton, N. J. Shah, M. A. Quadir, Z. J. Deng, Z. Poon et al., Osteotropic Therapy via Targeted Layer-by-Layer Nanoparticles, Adv. Healthcare Mater, vol.3, issue.6, pp.867-875, 2014.

S. P. Zinnen, A. Karpeisky, D. D. Van-hoff, L. Plekhova, A. et al., First-in-Human Phase I Study of MBC-11, a Novel Bone-Targeted Cytarabine-Etidronate Conjugate in Patients with Cancer-Induced Bone Disease, Oncologist, vol.24, p.303, 2019.

W. Ye, Y. Zhao, R. Na, F. Li, Q. Mei et al., , 2015.

, Bone Metastases by a PH-Sensitive Conjugation, J. Pharm. Sci, vol.104, issue.7, pp.2293-2303

K. Hochdorffer, K. Abu-ajaj, C. Schafer-obodozie, and F. Kratz, Development of Novel Bisphosphonate Prodrugs of Doxorubicin for Targeting Bone Metastases That Are Cleaved PH Dependently or by Cathepsin B:Synthesis, Cleavage Properties, and Binding Properties to Hydroxyapatite As Well As Bone Matrix, J. Med. Chem, vol.55, issue.17, pp.7502-7515, 2012.

F. Kratz and . Bisphosphonate-prodrugs, International Patent WO2011023367A3

M. Egorov, J. Goujon, L. Bot, R. , D. et al., , 2016.

, Hydrosoluble Hydroxy-Bisphosphonic Derivatives of Doxorubicin PCT Int. Appl. WO

M. Egorov, J. Goujon, L. Bot, and R. , Bifunctional Hydroxy-Bisphosphonic Acid Derivatives, PCT Int. Appl. WO, 2012.

M. Egorov, Y. Fortun, D. Heymann, J. Lebreton, M. Mathe et al., Hydroxy-Bisphosphonic Acid Derivatives as Vectors for Therapeutic and Diagnostic Targeting of Bone Tissue, PCT Int. Appl. WO, 2009.

M. Egorov, S. Aoun, M. Padrines, F. Redini, D. Heymann et al., A One-Pot Synthesis of 1-Hydroxy-1,1-Bis(Phosphonic Acid)s Starting from the Corresponding Carboxylic Acids, Eur. J. Org. Chem, pp.7148-7154, 2011.
URL : https://hal.archives-ouvertes.fr/hal-02143149

M. Lecouvey, A Mild and Efficient One-Pot Synthesis of 1-Hydroxymethylene-1,1-Bisphosphonic Acids. Preparation of New Tripod Ligands, Tetrahedron Lett, vol.42, p.8475, 2001.

M. Anderson, A. Moshnikova, D. M. Engelman, Y. K. Reshetnyak, and O. A. Andreev, Probe for the Measurement of Cell Surface PH in Vivo and Ex Vivo, Proc. Natl. Acad. Sci. U. S. A, vol.113, issue.29, pp.8177-8181, 2016.

P. Vaupel, F. Kallinowski, and P. Okunieff, Blood Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human Tumors, Cancer Res, vol.49, issue.23, pp.6449-6465, 1989.

I. A. Silver, R. J. Murrills, and D. J. Etherington, , 1988.

, Microelectrode Studies on the Acid Microenvironment beneath Adherent Macrophages and Osteoclasts. Exp. Cell Res, vol.175, issue.2, pp.266-276

M. Susa, A. K. Iyer, K. Ryu, F. J. Hornicek, H. Mankin et al., Doxorubicin Loaded Polymeric Nanoparticulate Delivery System to Overcome Drug Resistance in Osteosarcoma, BMC Cancer, vol.9, p.399, 2009.

F. P. Coxon, K. Thompson, A. J. Roelofs, F. H. Ebetino, and M. J. Rogers, Visualizing Mineral Binding and Uptake of Bisphosphonate by Osteoclasts and Non-Resorbing Cells, Bone, vol.42, issue.5, pp.848-860, 2008.

A. Verhulst, S. Sun, C. E. Mckenna, and P. C. Ddhaese, Endocytotic Uptake of Zoledronic Acid by Tubular Cells May Explain Its Renal Effects in Cancer Patients Receiving High Doses of the Compound, PLoS One, vol.10, issue.3, p.121861, 2015.

K. Thompson, M. J. Rogers, F. P. Coxon, and J. C. Crockett, Cytosolic Entry of Bisphosphonate Drugs Requires Acidification of Vesicles after Fluid-Phase Endocytosis, Mol. Pharmacol, vol.69, issue.5, pp.1624-1632, 2006.

C. Bertazzoli, C. Rovero, L. Ballerini, B. Lux, F. Balconi et al., Toxicol. Appl. Pharmacol, vol.79, issue.3, pp.412-422, 1985.

F. Kratz, G. Ehling, H. Kauffmann, and C. Unger, Acute and Repeat-Dose Toxicity Studies of the (6-Maleimidocaproyl)Hydrazone Derivative of Doxorubicin (DOXO-EMCH), an Albumin-Binding Prodrug of the Anticancer Agent Doxorubicin, Hum. Exp. Toxicol, vol.26, issue.1, pp.19-35, 2007.

V. G. Desai, E. H. Herman, C. L. Moland, W. S. Branham, S. M. Lewis et al., Development of Doxorubicin-Induced Chronic Cardiotoxicity in the B6C3F1Mouse Model, Toxicol. Appl. Pharmacol, vol.266, issue.1, pp.109-121, 2013.

A. A. El-mabhouh and J. R. Mercer, -Labelled Gemcitabine/Bisphosphonate (Gem/BP): A Multi-Functional, Bone-Specific Agent as a Potential Treatment for Bone Metastases, Eur. J. Nucl. Med. Mol. Imaging, vol.35, issue.7, pp.1240-1248, 2008.

E. Palma, J. D. Correia, B. L. Oliveira, L. Gano, I. C. Santos et al., (CO)3-Labeled Pamidronate and Alendronate for Bone Imaging, Dalton Trans, vol.40, issue.12, pp.2787-2796, 2011.

H. Xie, G. Chen, Y. , and R. N. , Design, Synthesis, and Pharmacokinetics of a Bone-Targeting Dual-Action Prodrug for the Treatment of Osteoporosis, J. Med. Chem, vol.60, issue.16, pp.7012-7028, 2017.

R. L. Souhami, A. W. Craft, J. W. Van-der-eijken, M. Der-nooij, D. Spooner et al., Randomised Trial of Two Regimens of Chemotherapy in Operable Osteosarcoma: A Study of the European Osteosarcoma Intergroup, Lancet, vol.350, issue.9082, pp.911-917, 1997.

C. Jasmin, M. Allouche, J. G. Jude, B. Klein, J. P. Thie?y et al., An experimental model of osteosarcomas in rats, Sem Hop, vol.58, pp.1684-1689, 1982.